163-576: 3HO5 , 3M1N , 3MXW 6469 20423 ENSG00000164690 ENSMUSG00000002633 Q15465 Q62226 NM_000193 NM_001310462 NM_009170 NP_000184 NP_001297391 NP_033196 Sonic hedgehog protein ( SHH ) is encoded for by the SHH gene . The protein is named after the video game character Sonic the Hedgehog . This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and
326-514: A concentration gradient within the neural tube. Although there is no direct evidence of a SHH gradient , there is indirect evidence via the visualization of Patched ( Ptc ) gene expression, which encodes for the ligand binding domain of the SHH receptor throughout the ventral neural tube. In vitro studies show that incremental two- and threefold changes in SHH concentration give rise to motor neuron and different interneuronal subtypes as found in
489-432: A homozygous embryo. The zebrafish embryos are transparent and they develop outside of the uterus, which allows scientists to study the details of development starting from fertilization and continuing throughout development. The zebrafish is also demonstrably similar to mammalian models and humans in toxicity testing, and exhibits a diurnal sleep cycle with similarities to mammalian sleep behavior. However, zebrafish are not
652-588: A promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription. The recognition typically occurs as a consensus sequence like the TATA box . A gene can have more than one promoter, resulting in messenger RNAs ( mRNA ) that differ in how far they extend in the 5' end. Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at
815-605: A solute carrier that appeared to be required for melanin production, and confirmed its function with a Morpholino knockdown. The orthologous gene was then characterized in humans and a one base pair difference was found to strongly segregate fair-skinned Europeans and dark-skinned Africans. Zebrafish with the nacre mutation have since been bred with fish with a roy orbison (roy) mutation to make Casper strain fish that have no melanophores or iridophores, and are transparent into adulthood. These fish are characterized by uniformly pigmented eyes and translucent skin. Transgenesis
978-509: A " start codon ", and three " stop codons " indicate the beginning and end of the protein coding region . There are 64 possible codons (four possible nucleotides at each of three positions, hence 4 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms. Zebra Danio The zebrafish ( Danio rerio )
1141-538: A character from Beatrix Potter 's books for children) and ihha and ihhb (formerly described as echidna hedgehog , named for the spiny anteater and not for the character Knuckles the Echidna in the Sonic franchise ). Of the hh homologues, SHH has been found to have the most critical roles in development, acting as a morphogen involved in patterning many systems—including the anterior pituitary , pallium of
1304-473: A concentration-dependent manner, so that a high concentration of SHH results in a local inhibition of cellular proliferation . This inhibition causes the floor plate to become thin compared to the lateral regions of the neural tube . Lower concentration of SHH results in cellular proliferation and induction of various ventral neural cell types. Once the floor plate is established, cells residing in this region will subsequently express SHH themselves, generating
1467-445: A continuous messenger RNA , referred to as a polycistronic mRNA . The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region , and represses transcription of
1630-413: A daily basis. Females are able to spawn at intervals of two to three days, laying hundreds of eggs in each clutch . Upon release, embryonic development begins; in absence of sperm, growth stops after the first few cell divisions. Fertilized eggs almost immediately become transparent, a characteristic that makes D. rerio a convenient research model species . Sex determination of common laboratory strains
1793-497: A dedicated online database of genetic, genomic, and developmental information, the Zebrafish Information Network (ZFIN). The Zebrafish International Resource Center (ZIRC) is a genetic resource repository with 29,250 alleles available for distribution to the research community. D. rerio is also one of the few fish species to have been sent into space . Research with D. rerio has yielded advances in
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#17327795798891956-498: A double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile . The expression of genes encoded in DNA begins by transcribing the gene into RNA , a second type of nucleic acid that is very similar to DNA, but whose monomers contain
2119-538: A failure of splitting in the cerebral hemispheres, as demonstrated in an experiment using SHH knock-out mice in which the forebrain midline failed to develop and instead only a single fused telencephalic vesicle resulted. Sonic hedgehog still plays a role in differentiation, proliferation, and maintenance of adult tissues. Abnormal activation of SHH signaling in adult tissues has been implicated in various types of cancers including breast , skin , brain , liver , gallbladder and many more. The hedgehog gene ( hh )
2282-488: A few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer . Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas
2445-434: A gene - surprisingly, there is no definition that is entirely satisfactory. A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere. The important parts of such definitions are: (1) that
2608-443: A gene can be found in the articles Genetics and Gene-centered view of evolution . The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics — the gene that is described in terms of DNA sequence. There are many different definitions of this gene — some of which are misleading or incorrect. Very early work in the field that became molecular genetics suggested
2771-573: A gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there's one other important part of the definition and it is emphasized in Kostas Kampourakis' book Making Sense of Genes . Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecules. With 'encoding information', I mean that
2934-410: A gene may be split across chromosomes but those transcripts are concatenated back together into a functional sequence by trans-splicing . It is also possible for overlapping genes to share some of their DNA sequence, either on opposite strands or the same strand (in a different reading frame, or even the same reading frame). In all organisms, two steps are required to read the information encoded in
3097-404: A gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA ( mRNA ). Second, that mRNA is translated to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression , and the resulting molecule
3260-411: A gene), DNA is first copied into RNA . RNA can be directly functional or be the intermediate template for the synthesis of a protein. The transmission of genes to an organism's offspring , is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype , that is specific to every given individual, within
3423-578: A gene: that of bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. An automated version of the Sanger method was used in early phases of the Human Genome Project . The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called
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#17327795798893586-439: A gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence. The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome . DNA packaged and condensed in this way is called chromatin . The manner in which DNA
3749-407: A group, males will mate with whichever females they can find. What attracts females is not currently understood. The presence of plants, even plastic plants, also apparently encourages spawning. Exposure to environmentally relevant concentrations of diisononyl phthalate (DINP), commonly used in a large variety of plastic items, disrupt the endocannabinoid system and thereby affect reproduction in
3912-448: A high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently. Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters. Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act by binding to transcription factors which then cause
4075-597: A laboratory animal was pioneered by the American molecular biologist George Streisinger and his colleagues at the University of Oregon in the 1970s and 1980s; Streisinger's zebrafish clones were among the earliest successful vertebrate clones created. Its importance has been consolidated by successful large-scale forward genetic screens (commonly referred to as the Tübingen/Boston screens). The fish has
4238-453: A low concentration of SHH for a relatively short time and express the transcription factor Olig2. The expression of Olig2 rapidly expands in a dorsal direction concomitantly with the continuous dorsal extension of the SHH gradient over time. However, as the morphogenetic front of SHH ligand moves and begins to grow more concentrated, cells that are exposed to higher levels of the ligand respond by switching off Olig2 and turning on Nkx2.2, creating
4401-477: A mutation in a sonic hedgehog gene might not be well received in a discussion of a serious disorder with a patient or their family. This controversy has largely died down, and the name is now generally seen as a humorous relic of the time before the rise of fast, cheap complete genome sequencing and standardized nomenclature. The problem of the "inappropriateness" of the names of genes such as " Mothers against decapentaplegic ," " Lunatic fringe ," and "Sonic hedgehog"
4564-572: A new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century. Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g. RNA viruses ), bacterial operons are multiple protein-coding regions transcribed into single large mRNAs, alternative splicing enables
4727-460: A new strain of zebrafish, named Casper, whose adult bodies had transparent skin. This allows for detailed visualization of cellular activity, circulation, metastasis and many other phenomena. In 2019 researchers published a crossing of a prkdc and a IL2rga strain that produced transparent, immunodeficient offspring, lacking natural killer cells as well as B - and T-cells . This strain can be adapted to 37 °C (99 °F) warm water and
4890-592: A number of commercially available global platforms exist for analysis of both gene expression by microarrays and promoter regulation using ChIP-on-chip . The Wellcome Trust Sanger Institute started the zebrafish genome sequencing project in 2001, and the full genome sequence of the Tuebingen reference strain is publicly available at the National Center for Biotechnology Information (NCBI)'s Zebrafish Genome Page . The zebrafish reference genome sequence
5053-400: A process known as RNA splicing . Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites , where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from
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5216-419: A protein-coding gene consists of many elements of which the actual protein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA. All genes are associated with regulatory sequences that are required for their expression. First, genes require
5379-460: A sex-specific manner. Zebrafish feeding practices vary significantly across different developmental stages, reflecting their changing nutritional needs. For newly hatched larvae, which begin feeding at approximately 5 days post-fertilization (dpf), small live prey such as Paramecium or rotifers are commonly used until they reach 9–15 dpf. This early diet is crucial for their growth and survival, as these small organisms provide essential nutrients. As
5542-406: A sharp boundary between the cells expressing the transcription factor Nkx2.2 ventral to the cells expressing Olig2. It is in this way that each of the domains of the six progenitor cell populations are thought to be successively patterned throughout the neural tube by the SHH concentration gradient. Mutual inhibition between pairs of transcription factors expressed in neighboring domains contributes to
5705-412: A single genomic region to encode multiple district products and trans-splicing concatenates mRNAs from shorter coding sequence across the genome. Since molecular definitions exclude elements such as introns, promotors, and other regulatory regions , these are instead thought of as "associated" with the gene and affect its function. An even broader operational definition is sometimes used to encompass
5868-490: A sliding bottom insert, which reduces the depth of the pool to simulate the shore of a river. Zebrafish spawn best in the morning due to their Circadian rhythms . Researchers have been able to collect 10,000 embryos in 10 minutes using this method. In particular, one pair of adult fish is capable of laying 200–300 eggs in one morning in approximately 5 to 10 at time. Male zebrafish are furthermore known to respond to more pronounced markings on females, i.e., "good stripes", but in
6031-412: A specialised protein , known as fibroblast growth factor , to ensure their spinal cords heal without glial scarring after injury. In addition, hair cells of the posterior lateral line have also been found to regenerate following damage or developmental disruption. Study of gene expression during regeneration has allowed for the identification of several important signaling pathways involved in
6194-475: A strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along
6357-437: A study was published about zebrafishes' capacity for episodic memory . The individuals showed a capacity to remember context with respect to objects, locations and occasions (what, when, where). Episodic memory is a capacity of explicit memory systems, typically associated with conscious experience . The Mauthner cells integrate a wide array of sensory stimuli to produce the escape reflex . Those stimuli are found to include
6520-409: A true gene, by this definition, one has to prove that the transcript has a biological function. Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). This was based on the idea that the gene was the DNA that was directly responsible for production of
6683-512: A universally ideal research model; there are a number of disadvantages to their scientific use, such as the absence of a standard diet and the presence of small but important differences between zebrafish and mammals in the roles of some genes related to human disorders. Zebrafish have the ability to regenerate their heart and lateral line hair cells during their larval stages. The cardiac regenerative process likely involves signaling pathways such as Notch and Wnt ; hemodynamic changes in
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6846-422: Is 16,596 base pairs. This is within 100 base pairs of other related species of fish, and it is notably only 18 pairs longer than the goldfish ( Carassius auratus ) and 21 longer than the carp ( Cyprinus carpio ). Its gene order and content are identical to the common vertebrate form of mitochondrial DNA. It contains 13 protein -coding genes and a noncoding control region containing the origin of replication for
7009-562: Is a freshwater fish belonging to the minnow family ( Cyprinidae ) of the order Cypriniformes . Native to South Asia, it is a popular aquarium fish , frequently sold under the trade name zebra danio (and thus often called a " tropical fish " although it is both tropical and subtropical ). The zebrafish is an important and widely used vertebrate model organism in scientific research, particularly developmental biology , but also gene function, oncology , teratology , and drug development , in particular pre-clinical development . It
7172-455: Is a condition that affects the eyes, which results in small, underdeveloped tissues in one or both eyes. This can lead to issues ranging from a coloboma to a single small eye to the absence of eyes altogether. Holoprosencephaly is a condition most commonly caused by a mutation of the SHH gene that causes improper separation or turn of the left and right brain and facial dysmorphia. Many systems and structures rely heavily on proper expression of
7335-472: Is a crucial mediator of hedgehog ( Hh ) signaling in Drosophila . In vertebrates, three different Gli proteins are present, viz. Gli1 , Gli2 and Gli3 , which are expressed in the neural tube. Mice mutants for Gli1 show normal spinal cord development, suggesting that it is dispensable for mediating SHH activity. However, Gli2 mutant mice show abnormalities in the ventral spinal cord, with severe defects in
7498-493: Is a popular approach to study the function of genes in zebrafish. Construction of transgenic zebrafish is rather easy by a method using the Tol2 transposon system. Tol2 element which encodes a gene for a fully functional transposase capable of catalyzing transposition in the zebrafish germ lineage. Tol2 is the only natural DNA transposable element in vertebrates from which an autonomous member has been identified. Examples include
7661-611: Is a signaling center that is responsible for the patterned development of the upper jaw, regulates craniofacial development mediating through the miR-199 family in the FEZ. Specifically, SHH-dependent signals from the brain regulate genes of the miR-199 family with downregulations of the miR-199 genes increasing SHH expression and resulting in wider faces, while upregulations of the miR-199 genes decrease SHH expression resulting in narrow faces. SHH plays an important role in organogenesis and, most importantly, craniofacial development. Being that SHH
7824-434: Is a signaling molecule, it primarily works by diffusion along a concentration gradient, affecting cells in different manners. In early tooth development, SHH is released from the primary enamel knot —a signaling center—to provide positional information in both a lateral and planar signaling pattern in tooth development and regulation of tooth cusp growth. SHH in particular is needed for growth of epithelial cervical loops, where
7987-508: Is a spotted colour morph of the zebrafish which arose due to a pigment mutation. Xanthistic forms of both the zebra and leopard pattern, along with long-finned strains, have been obtained via selective breeding programs for the aquarium trade. Various transgenic and mutant strains of zebrafish were stored at the China Zebrafish Resource Center (CZRC), a non-profit organization, which was jointly supported by
8150-405: Is able to integrate into most cells of the embryo. A known problem with gene knockdowns is that, because the genome underwent a duplication after the divergence of ray-finned fishes and lobe-finned fishes , it is not always easy to silence the activity of one of the two gene paralogs reliably due to complementation by the other paralog. Despite the complications of the zebrafish genome ,
8313-627: Is added to the C-terminus of SHH-N. Thus, the C-terminal domain acts as an intein and a cholesterol transferase. Another hydrophobic moiety , a palmitate , is added to the alpha-amine of N-terminal cysteine of SHH-N. This modification is required for efficient signaling, resulting in a 30-fold increase in potency over the non-palmitylated form and is carried out by a member of the membrane-bound O-acyltransferase family Protein-cysteine N-palmitoyltransferase HHAT . A potential inhibitor of
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#17327795798898476-428: Is also notable for its regenerative abilities, and has been modified by researchers to produce many transgenic strains. The zebrafish is a derived member of the genus Brachydanio , of the family Cyprinidae . It has a sister-group relationship with Danio aesculapii . Zebrafish are also closely related to the genus Devario , as demonstrated by a phylogenetic tree of close species. The zebrafish
8639-658: Is annotated as part of the Ensembl project , and is maintained by the Genome Reference Consortium . In 2009, researchers at the Institute of Genomics and Integrative Biology in Delhi, India, announced the sequencing of the genome of a wild zebrafish strain, containing an estimated 1.7 billion genetic letters. The genome of the wild zebrafish was sequenced at 39-fold coverage. Comparative analysis with
8802-456: Is called a gene product . The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code . Sets of three nucleotides, known as codons , each correspond to a specific amino acid. The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4 (see Crick, Brenner et al. experiment ). Additionally,
8965-463: Is important to note that SHH is not the only signaling molecule exerting an effect on the developing neural tube. Many other molecules, pathways and mechanisms are active (e.g., RA , FGF , BMP ), and complex interactions between SHH and other molecules are possible. BMPs are suggested to play a critical role in determining the sensitivity of neural cell to SHH signaling. Evidence supporting this comes from studies using BMP inhibitors that ventralize
9128-502: Is indicative of holoprosencephaly . However, SHH activates downstream molecules of Gli2 and Gli3. Mutant Gli2 and Gli3 embryos have abnormal development of incisors that are arrested in early tooth development as well as small molars. Although SHH is most commonly associated with brain and limb digit development, it is also important in lung development. Studies using qPCR and knockouts have demonstrated that SHH contributes to embryonic lung development. The mammalian lung branching occurs in
9291-526: Is largely avoided by using standardized abbreviations when speaking with patients and their families. Gene In biology , the word gene has two meanings. The Mendelian gene is a basic unit of heredity . The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA . There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of RNA or protein from
9454-497: Is linked to male infertility. The researchers cloned oestrogen-sensitive genes and injected them into the fertile eggs of zebrafish. The modified fish turned green if placed into water that was polluted by oestrogen. In 2015, researchers at Brown University discovered that 10% of zebrafish genes do not need to rely on the U2AF2 protein to initiate RNA splicing . These genes have the DNA base pairs AC and TG as repeated sequences at
9617-566: Is more local, with scattered records from the Western and Eastern Ghats regions. It has frequently been said to occur in Myanmar (Burma), but this is entirely based on pre-1930 records and likely refers to close relatives only described later, notably Danio kyathit . Likewise, old records from Sri Lanka are highly questionable and remain unconfirmed. Zebrafish have been introduced to California, Connecticut, Florida and New Mexico in
9780-486: Is mutated or absent, the protein Sonic Hedgehog cannot do its job properly. Sonic hedgehog contributes to cell growth, cell specification and formation, structuring and organization of the body plan. This protein functions as a vital morphogenic signaling molecule and plays an important role in the formation of many different structures in developing embryos. The SHH gene affects several major organ systems, such as
9943-818: Is native to freshwater habitats in South Asia where it is found in India, Pakistan, Bangladesh, Nepal and Bhutan. The northern limit is in the South Himalayas , ranging from the Sutlej river basin in the Pakistan–India border region to the state of Arunachal Pradesh in northeast India. Its range is concentrated in the Ganges and Brahmaputra River basins, and the species was first described from Kosi River (lower Ganges basin) of India. Its range further south
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#173277957988910106-400: Is nearly the same for all known organisms. The total complement of genes in an organism or cell is known as its genome , which may be stored on one or more chromosomes . A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. The region of the chromosome at which a particular gene is located is called its locus . Each locus contains one allele of
10269-403: Is still part of the definition of a gene in most textbooks. For example, The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of
10432-399: Is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression . In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins , telomeres , and
10595-474: Is strongly expressed in the buds of the fetal lungs but low in the developing bronchi. Mice who are deficient in SHH can develop tracheoesophageal fistula (abnormal connection of the esophagus and trachea). Additionally, a double (SHH-/- ) knockout mouse model exhibited poor lung development. The lungs of the SHH double knockout failed to undergo lobation and branching (i.e., the abnormal lungs only developed one branch, compared to an extensively branched phenotype of
10758-455: Is the initial groundwork of the vertebrate CNS , and the floor plate is a specialized structure, located at the ventral midpoint of the neural tube. Evidence supporting the notochord as the signaling center comes from studies in which a second notochord is implanted near a neural tube in vivo, leading to the formation of an ectopic floor plate within the neural tube. Sonic hedgehog is the secreted protein that mediates signaling activities of
10921-405: Is thought that the SHH gradient works to elicit multiple different cell fates by a concentration- and time-dependent mechanism that induces a variety of transcription factors in the ventral progenitor cells . Each of the ventral progenitor domains expresses a highly individualized combination of transcription factors—Nkx2.2, Olig2, Nkx6.1, Nkx6.2, Dbx1, Dbx2, Irx3, Pax6, and Pax7—that is regulated by
11084-407: Is to reduce gene expression or modify splicing using Morpholino antisense technology. Morpholino oligonucleotides (MO) are stable, synthetic macromolecules that contain the same bases as DNA or RNA; by binding to complementary RNA sequences, they can reduce the expression of specific genes or block other processes from occurring on RNA. MO can be injected into one cell of an embryo after
11247-407: Is usually some vegetation, either submerged or overhanging from the banks, and the bottom is sandy, muddy or silty, often mixed with pebbles or gravel. In surveys of zebrafish locations throughout much of its Bangladeshi and Indian distribution, the water had a near-neutral to somewhat basic pH and mostly ranged from 16.5 to 34 °C (61.7–93.2 °F) in temperature. One unusually cold site
11410-414: Is very rapid, and its embryos are relatively large, robust, and transparent, and able to develop outside their mother. Furthermore, well-characterized mutant strains are readily available. Other advantages include the species' nearly constant size during early development, which enables simple staining techniques to be used, and the fact that its two-celled embryo can be fused into a single cell to create
11573-586: The Carp (including Grass Carp, Ctenopharyngodon idella ) and Milkfish ( Chanos chanos ) which are quite close, both being in the Cyprinidae . However it should also be noted that Danio consistently proves to be a useful model for mammals in many cases and there is dramatically more genetic distance between them than between Danio and any farmed fish. In a glucocorticoid receptor -defective mutant with reduced exploratory behavior , fluoxetine rescued
11736-634: The Ministry of Science and Technology of China and the Chinese Academy of Sciences . The Zebrafish Information Network ( ZFIN ) provides up-to-date information about current known wild-type (WT) strains of D. rerio , some of which are listed below. Hybrids between different Danio species may be fertile: for example, between D. rerio and D. nigrofasciatus . D. rerio is a common and useful scientific model organism for studies of vertebrate development and gene function. Its use as
11899-410: The SHH gene and subsequent sonic hedgehog protein, earning it the distinction of being an essential gene to development. The sonic hedgehog (SHH) signaling molecule assumes various roles in patterning the central nervous system (CNS) during vertebrate development . One of the most characterized functions of SHH is its role in the induction of the floor plate and diverse ventral cell types within
12062-511: The aging process. The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division . Prokaryotes ( bacteria and archaea ) typically store their genomes on a single, large, circular chromosome . Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes. Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids , which usually encode only
12225-401: The anal fin origin. The zebrafish can reach up to 4–5 cm (1.6–2.0 in) in length, although they typically are 1.8–3.7 cm (0.7–1.5 in) in the wild with some variations depending on location. Its lifespan in captivity is around two to three years, although in ideal conditions, this may be extended to over five years. In the wild it is typically an annual species. In 2015,
12388-411: The apical ectodermal ridge . Sonic hedgehog has also been shown to act as an axonal guidance cue . It has been demonstrated that SHH attracts commissural axons at the ventral midline of the developing spinal cord. Specifically, SHH attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at higher concentrations. The absence (non-expression) of SHH has been shown to control
12551-401: The central dogma of molecular biology , which states that proteins are translated from RNA , which is transcribed from DNA . This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses . The modern study of genetics at the level of DNA is known as molecular genetics . In 1972, Walter Fiers and his team were the first to determine the sequence of
12714-419: The centromere . Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication . The length of the telomeres decreases each time the genome is replicated and has been implicated in
12877-444: The gene pool of the population of a given species . The genotype, along with environmental and developmental factors, ultimately determines the phenotype of the individual. Most biological traits occur under the combined influence of polygenes (a set of different genes) and gene–environment interactions . Some genetic traits are instantly visible, such as eye color or the number of limbs, others are not, such as blood type ,
13040-469: The lateral line signals by McHenry et al. 2009 and visual signals consistent with looming objects by Temizer et al. 2015, Dunn et al. 2016, and Yao et al. 2016. The approximate generation time for Danio rerio is three months. A male must be present for ovulation and spawning to occur. Zebrafish are asynchronous spawners and under optimal conditions (such as food availability and favorable water parameters) can spawn successfully frequently, even on
13203-554: The modern synthesis , a term introduced by Julian Huxley . This view of evolution was emphasized by George C. Williams ' gene-centric view of evolution . He proposed that the Mendelian gene is a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." Related ideas emphasizing the centrality of Mendelian genes and the importance of natural selection in evolution were popularized by Richard Dawkins . The development of
13366-440: The neural tube . The notochord —a structure derived from the axial mesoderm —produces SHH, which travels extracellularly to the ventral region of the neural tube and instructs those cells to form the floor plate. Another view of floor plate induction hypothesizes that some precursor cells located in the notochord are inserted into the neural plate before its formation, later giving rise to the floor plate. The neural tube itself
13529-475: The neutral theory of evolution in the late 1960s led to the recognition that random genetic drift is a major player in evolution and that neutral theory should be the null hypothesis of molecular evolution. This led to the construction of phylogenetic trees and the development of the molecular clock , which is the basis of all dating techniques using DNA sequences. These techniques are not confined to molecular gene sequences but can be used on all DNA segments in
13692-750: The operon ; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon ). The products of operon genes typically have related functions and are involved in the same regulatory network . Though many genes have simple structures, as with much of biology, others can be quite complex or represent unusual edge-cases. Eukaryotic genes often have introns that are much larger than their exons, and those introns can even have other genes nested inside them . Associated enhancers may be many kilobase away, or even on entirely different chromosomes operating via physical contact between two chromosomes. A single gene can encode multiple different functional products by alternative splicing , and conversely
13855-432: The replication crisis in biomedical research. Genetic differences in wild-type lines among populations maintained at different research institutions have been demonstrated using both Single-nucleotide polymorphisms and microsatellite analysis. Due to their fast and short life cycles and relatively large clutch sizes, D. rerio or zebrafish are a useful model for genetic studies. A common reverse genetics technique
14018-456: The ventral neural tube makes it a prime example of a morphogen . In vertebrates, SHH signaling in the ventral portion of the neural tube is most notably responsible for the induction of floor plate cells and motor neurons . SHH emanates from the notochord and ventral floor plate of the developing neural tube to create a concentration gradient that spans the dorso-ventral axis and is antagonized by an inverse Wnt gradient, which specifies
14181-410: The 32-cell stage, reducing gene expression in only cells descended from that cell. However, cells in the early embryo (less than 32 cells) are permeable to large molecules, allowing diffusion between cells. Guidelines for using Morpholinos in zebrafish describe appropriate control strategies. Morpholinos are commonly microinjected in 500pL directly into 1–2 cell stage zebrafish embryos. The morpholino
14344-404: The DNA helix that produces a functional RNA molecule constitutes a gene. We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of
14507-450: The DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function. The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as
14670-766: The DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes , RNA-binding proteins , miRNA , as well as terminator , and start and stop codons . In addition, most eukaryotic open reading frames contain untranslated introns , which are removed and exons , which are connected together in
14833-523: The Hedgehog signaling pathway has been found and dubbed "Robotnikinin"—after Sonic the Hedgehog's nemesis and the main antagonist of the Sonic the Hedgehog game series, Dr. Ivo "Eggman" Robotnik . The gene has been linked to a condition known as holoprosencephaly , which can result in severe brain, skull and facial defects, causing a few clinicians and scientists to criticize the name on the grounds that it sounds too frivolous. It has been noted that mention of
14996-455: The SHH gradient. These transcription factors are induced sequentially along the SHH concentration gradient with respect to the amount and time of exposure to SHH ligand. As each population of progenitor cells responds to the different levels of SHH protein, they begin to express a unique combination of transcription factors that leads to neuronal cell fate differentiation. This SHH-induced differential gene expression creates sharp boundaries between
15159-550: The United States, presumably by deliberate release by aquarists or by escape from fish farms . The New Mexico population had been extirpated by 2003 and it is unclear if the others survive, as the last published records were decades ago. Elsewhere the species has been introduced to Colombia and Malaysia. Zebrafish typically inhabit moderately flowing to stagnant clear water of quite shallow depth in streams, canals, ditches, oxbow lakes , ponds and rice paddies . There
15322-399: The absence of an immune system makes the use of patient derived xenografts possible. In January 2013, Japanese scientists genetically modified a transparent zebrafish specimen to produce a visible glow during periods of intense brain activity. In January 2007, Chinese researchers at Fudan University genetically modified zebrafish to detect oestrogen pollution in lakes and rivers, which
15485-532: The activation function of Gli3, but this activity is not strong enough. The graded concentration of SHH gives rise to graded activity of Gli 2 and Gli3, which promote ventral and dorsal neuronal subtypes in the ventral spinal cord. Evidence from Gli3 and SHH/Gli3 mutants show that SHH primarily regulates the spatial restriction of progenitor domains rather than being inductive, as SHH/Gli3 mutants show intermixing of cell types. SHH also induces other proteins with which it interacts, and these interactions can influence
15648-457: The activity of Rb seems to allow cells to divide. Therefore, sonic hedgehog—identified as an important regulator of Rb—may also prove to be an important feature in regrowing hair cells after damage. SHH is important for regulating dermal adipogenesis by hair follicle transit-amplifying cells (HF-TACs). Specifically, SHH induces dermal angiogenesis by acting directly on adipocyte precursors and promoting their proliferation through their expression of
15811-433: The adenines of one strand are paired with the thymines of the other strand, and so on. Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose ; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end . The two strands of
15974-529: The alleles. There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories, the Mendelian gene or the molecular gene. The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. This is the gene described in The Selfish Gene . More thorough discussions of this version of
16137-434: The artificial interaction produced between LEF1 and Catenin beta-1 /β-catenin/ CTNNB1 . Dorsky et al. 2002 investigated the developmental role of Wnt by transgenically expressing a Lef1/β-catenin reporter. There are well-established protocols for editing zebrafish genes using CRISPR-Cas9 and this tool has been used to generate genetically modified models. In 2008, researchers at Boston Children's Hospital developed
16300-402: The brain, spinal cord , lungs , teeth and the thalamus by the zona limitans intrathalamica . In vertebrates, the development of limbs and digits depends on the secretion of sonic hedgehog by the zone of polarizing activity , located on the posterior side of the embryonic limb bud . Mutations in the human sonic hedgehog gene SHH cause holoprosencephaly type 3 HPE3, as a result of
16463-402: The complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. The existence of discrete inheritable units
16626-399: The concept that one gene makes one protein (originally 'one gene - one enzyme'). However, genes that produce repressor RNAs were proposed in the 1950s and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes. This idea of two kinds of genes
16789-783: The damaged heart are sensed by ventricular endothelial cells and their associated cardiac cilia by way of the mechanosensitive ion channel TRPV4 , subsequently facilitating the Notch signaling pathway via KLF2 and activating various downstream effectors such as BMP-2 and HER2/neu . In 2011, the British Heart Foundation ran an advertising campaign publicising its intention to study the applicability of this ability to humans, stating that it aimed to raise £50 million in research funding. Zebrafish have also been found to regenerate photoreceptor cells and retinal neurons following injury, which has been shown to be mediated by
16952-424: The dedifferentiation and proliferation of Müller glia . Researchers frequently amputate the dorsal and ventral tail fins and analyze their regrowth to test for mutations. It has been found that histone demethylation occurs at the site of the amputation, switching the zebrafish's cells to an "active", regenerative, stem cell-like state. In 2012, Australian scientists published a study revealing that zebrafish use
17115-492: The detrimental effects of inbreeding depression . Inbreeding depression is predominantly caused by the homozygous expression of recessive deleterious alleles. For zebrafish, inbreeding depression might be expected to be more severe in stressful environments, including those caused by anthropogenic pollution . Exposure of zebrafish to environmental stress induced by the chemical clotrimazole, an imidazole fungicide used in agriculture and in veterinary and human medicine, amplified
17278-516: The development of sharp boundaries; however, in some cases, inhibitory relationship has been found even between pairs of transcription factors from more distant domains. Particularly, NKX2-2 expressed in the V3 domain is reported to inhibit IRX3 expressed in V2 and more dorsal domains, although V3 and V2 are separated by a further domain termed MN. SHH expression in the frontonasal ectodermal zone (FEZ), which
17441-424: The discrete domains of transcription factor expression, which ultimately patterns the ventral neural tube. The spatial and temporal aspect of the progressive induction of genes and cell fates in the ventral neural tube is illustrated by the expression domains of two of the most well-characterized transcription factors, Olig2 and Nkx2.2. Early in development, the cells at the ventral midline have only been exposed to
17604-524: The distinction between a heterozygote and homozygote , and the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance , which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis , from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). Darwin used
17767-441: The dorsal spinal cord. Higher concentrations of the SHH ligand are found in the most ventral aspects of the neural tube and notochord, while lower concentrations are found in the more dorsal regions of the neural tube. The SHH concentration gradient has been visualized in the neural tube of mice engineered to express a SHH::GFP fusion protein to show this graded distribution of SHH during the time of ventral neural tube patterning. It
17930-410: The early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA. Collectively, this body of research established
18093-448: The effects of inbreeding on key reproductive traits. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring. Zebrafish are common models for research into fish farming , including pathogens and parasites causing yield loss or spreading to adjacent wild populations. This usefulness is less than it might be due to Danio ' s taxonomic distance from
18256-402: The embryos to be covered with denticles, i.e. small pointy projections resembling the spikes of a hedgehog . Investigations aimed at finding a hedgehog equivalent in vertebrates by Philip Ingham , Andrew P. McMahon and Clifford Tabin revealed three homologous genes . Two of these genes, desert hedgehog and Indian hedgehog , were named for species of hedgehogs, while sonic hedgehog
18419-457: The ends of each intron . On the 3'ss (3' splicing site), the base pairs adenine and cytosine alternate and repeat, and on the 5'ss (5' splicing site), their complements thymine and guanine alternate and repeat as well. They found that there was less reliance on U2AF2 protein than in humans, in which the protein is required for the splicing process to occur. The pattern of repeating base pairs around introns that alters RNA secondary structure
18582-430: The epithelium of the developing bronchi and lungs. SHH expressed throughout the foregut endoderm (innermost of three germ layers) in the distal epithelium, where the embryonic lungs are developing. This suggests that SHH is partially responsible for the branching of the lungs. Further evidence of SHH's role in lung branching has been seen with qPCR. SHH expression occurs in the developing lungs around embryonic day 11 and
18745-522: The fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a recent article in American Scientist. ... to truly assess the potential significance of de novo genes, we relied on
18908-490: The fate of the neural plate cell for a given SHH concentration. On the other hand, mutation in BMP antagonists (e.g., noggin ) produces severe defects in the ventral-most characteristics of the spinal cord, followed by ectopic expression of BMP in the ventral neural tube. Interactions of SHH with Fgf and RA have not yet been studied in molecular detail. The concentration- and time-dependent, cell-fate-determining activity of SHH in
19071-503: The fields of developmental biology , oncology , toxicology , reproductive studies, teratology , genetics , neurobiology , environmental sciences , stem cell research, regenerative medicine , muscular dystrophies and evolutionary theory . As a model biological system, the zebrafish possesses numerous advantages for scientists. Its genome has been fully sequenced , and it has well-understood, easily observable and testable developmental behaviors. Its embryonic development
19234-409: The first species to be sold as GloFish (fluorescent colored fish). In late 2003, transgenic zebrafish that express green , red, and yellow fluorescent proteins became commercially available in the United States. The fluorescent strains are trade-named GloFish ; other cultivated varieties include "golden", "sandy", "longfin" and "leopard". The leopard danio, previously known as Danio frankei ,
19397-464: The first step in protein secretion . Once translocation is complete, the signal sequence is removed by signal peptidase in the ER. There, SHH undergoes autoprocessing to generate a 20 kDa N-terminal signaling domain (SHH-N) and a 25 kDa C-terminal domain with no known signaling role. The cleavage is catalysed by a protease within the C-terminal domain. During the reaction, a cholesterol molecule
19560-432: The floor plate and ventral-most interneurons (V3). Gli3 antagonizes SHH function in a dose -dependent manner, promoting dorsal neuronal subtypes. SHH mutant phenotypes can be rescued in a SHH/Gli3 double mutant . Gli proteins have a C-terminal activation domain and an N-terminal repressive domain. SHH is suggested to promote the activation function of Gli2 and inhibit repressive activity of Gli3. SHH also seems to promote
19723-413: The functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome). In spite of
19886-421: The genome. The vast majority of organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar ( 2-deoxyribose ), a phosphate group, and one of the four bases adenine , cytosine , guanine , and thymine . Two chains of DNA twist around each other to form a DNA double helix with
20049-421: The genomes of complex multicellular organisms , including humans, contain an absolute majority of DNA without an identified function. This DNA has often been referred to as " junk DNA ". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome , about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer. The structure of
20212-406: The growth of nascent hind limbs in cetaceans ( whales and dolphins ). The SHH gene is a member of the hedgehog gene family with five variations of DNA sequence alterations or splice variants. SHH is located on chromosome seven and initiates the production of Sonic Hedgehog protein. This protein sends short- and long-range signals to embryonic tissues to regulate development. If the SHH gene
20375-634: The heavy strand. In between a grouping of five tRNA genes, a sequence resembling vertebrate origin of light strand replication is found. It is difficult to draw evolutionary conclusions because it is difficult to determine whether base pair changes have adaptive significance via comparisons with other vertebrates' nucleotide sequences. T-boxes and homeoboxes are vital in Danio similarly to other vertebrates. The Bruce et al. team are known for this area, and in Bruce et al. 2003 & Bruce et al. 2005 uncover
20538-411: The larvae develop, from 15 dpf onwards, they are typically transitioned to a diet that includes brine shrimp nauplii and dry feeds, which are more nutritionally balanced and easier to manage in laboratory settings. For larvae aged 25 dpf, feeding rates can range from 50% to 300% of their body weight (BW) per day, depending on their size and growth requirements. As zebrafish grow into juveniles (30–90 dpf),
20701-400: The loss of the ventral midline. The sonic hedgehog transcription pathway has also been linked to the formation of specific kinds of cancerous tumors, including the embryonic cerebellar tumor and medulloblastoma , as well as the progression of prostate cancer tumours. For SHH to be expressed in the developing embryo limbs, a morphogen called fibroblast growth factors must be secreted from
20864-709: The most common aquaculture species. Because the most common are salmonids and cod in the Protacanthopterygii and sea bass , sea bream , tilapia , and flatfish , in the Percomorpha , zebrafish results may not be perfectly applicable. Various other models – Goldfish ( Carassius auratus ), Medaka ( Oryzias latipes ), Stickleback ( Gasterosteus aculeatus ), Roach ( Rutilus rutilus ), Pufferfish ( Takifugu rubripes ), Swordtail ( Xiphophorus hellerii ) – are less used normally but would be closer to particular target species. The only exception are
21027-460: The mother – will prevent initiation of the mesoderm or endoderm development processes in this species.) In 1999, the nacre mutation was identified in the zebrafish ortholog of the mammalian MITF transcription factor. Mutations in human MITF result in eye defects and loss of pigment, a type of Waardenburg Syndrome . In December 2005, a study of the golden strain identified the gene responsible for its unusual pigmentation as SLC24A5 ,
21190-590: The nature of their interaction with SHH, they are classified into two groups—class I and class II—and are composed of members from the Pax , Nkx , Dbx and Irx families. Class I proteins are repressed at different thresholds of SHH delineating ventral boundaries of progenitor domains , while class II proteins are activated at different thresholds of SHH delineating the dorsal limit of domains. Selective cross- repressive interactions between class I and class II proteins give rise to five cardinal ventral neuronal subtypes. It
21353-407: The nervous system, cardiovascular system, respiratory system and musculoskeletal system. Mutations in the SHH gene can cause malformation of components of these systems, which can result in major problems in the developing embryo. The brain and eyes, for example, can be significantly impacted by mutations in this gene and cause disorders such as Microphthalmia and Holoprosencephaly . Microphthalmia
21516-467: The normal exploratory behavior. This demonstrates relationships between glucocorticoids, fluoxetine, and exploration in this fish. Zebrafish have been used as a model for studying DNA repair pathways. Embryos of externally fertilized fish species, such as zebrafish during their development, are directly exposed to environmental conditions such as pollutants and reactive oxygen species that may cause damage to their DNA . To cope with such DNA damages,
21679-402: The notochord and floor plate. Studies involving ectopic expression of SHH in vitro and in vivo result in floor plate induction and differentiation of motor neuron and ventral interneurons . On the other hand, mice mutants for SHH lack ventral spinal cord characteristics. In vitro blocking of SHH signaling using antibodies against it shows similar phenotypes. SHH exerts its effects in
21842-413: The nucleus. Splicing, followed by CPA, generate the final mature mRNA , which encodes the protein or RNA product. Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have poly(A) tails. Many prokaryotic genes are organized into operons , with multiple protein-coding sequences that are transcribed as a unit. The genes in an operon are transcribed as
22005-428: The opportunity, adults eat hatchlings, which may be protected by separating the two groups with a net, breeding box or separate tank. In captivity, zebrafish live approximately forty-two months. Some captive zebrafish can develop a curved spine. They can range from a few centimeters to a few inches, and provide movement in a freshwater fish tank. The zebra danio was also used to make genetically modified fish and were
22168-466: The organization of the central nervous system, limbs, digits and many other parts of the body. Sonic hedgehog is a morphogen that patterns the developing embryo using a concentration gradient characterized by the French flag model . This model has a non-uniform distribution of SHH molecules which governs different cell fates according to concentration. Mutations in this gene can cause holoprosencephaly ,
22331-427: The outer and inner epitheliums join and form a reservoir for dental stem cells. After the primary enamel knots are apoptosed, the secondary enamel knots are formed. The secondary enamel knots secrete SHH in combination with other signaling molecules to thicken the oral ectoderm and begin patterning the complex shapes of the crown of a tooth during differentiation and mineralization. In a knockout gene model, absence of SHH
22494-429: The peroxisome proliferator-activated receptor γ (Pparg) gene. SHH undergoes a series of processing steps before it is secreted from the cell. Newly synthesised SHH weighs 45 kDa and is referred to as the preproprotein. As a secreted protein, it contains a short signal sequence at its N-terminus, which is recognised by the signal recognition particle during the translocation into the endoplasmic reticulum (ER),
22657-431: The phosphate–sugar backbone spiralling around the outside, and the bases pointing inward with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds , whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, be complementary , with their sequence of bases matching such that
22820-429: The process, such as Wnt signaling and Fibroblast growth factor . In probing disorders of the nervous system, including neurodegenerative diseases, movement disorders, psychiatric disorders and deafness, researchers are using the zebrafish to understand how the genetic defects underlying these conditions cause functional abnormalities in the human brain, spinal cord and sensory organs. Researchers have also studied
22983-584: The recommended feeding rate decreases to about 6–8% of their BW per day, with a focus on high-quality dry feeds that meet their protein and energy needs. Upon reaching adulthood (over 90 dpf), zebrafish typically require a feeding rate of around 5% of their BW per day. Throughout these stages, it is essential to adjust the particle size of the feed: less than 100 μm for newly hatched larvae, 100–200 μm for those between 16 and 30 dpf, and larger particles for juveniles and adults. This structured approach to feeding not only supports optimal growth and health but also enhances
23146-551: The reliability of experimental outcomes in research settings Zebrafish are hardy fish and considered good for beginner aquarists. Their enduring popularity can be attributed to their playful disposition, as well as their rapid breeding, aesthetics, cheap price and broad availability. They also do well in schools or shoals of six or more, and interact well with other fish species in the aquarium. However, they are susceptible to Oodinium or velvet disease, microsporidia ( Pseudoloma neurophilia ), and Mycobacterium species. Given
23309-431: The risk for specific diseases, or the thousands of basic biochemical processes that constitute life . A gene can acquire mutations in its sequence , leading to different variants, known as alleles , in the population . These alleles encode slightly different versions of a gene, which may cause different phenotypical traits. Genes evolve due to natural selection or survival of the fittest and genetic drift of
23472-509: The role of two of these elements in oocytes of this species. By interfering via a dominant nonfunctional allele and a morpholino they find the T-box transcription activator Eomesodermin and its target mtx2 – a transcription factor – are vital to epiboly . (In Bruce et al. 2003 they failed to support the possibility that Eomesodermin behaves like Vegt . Neither they nor anyone else has been able to locate any mutation which – in
23635-694: The sensitivity of a cell towards SHH. Hedgehog-interacting protein ( HHIP ) is induced by SHH, which in turn attenuates its signaling activity. Vitronectin is another protein that is induced by SHH; it acts as an obligate co-factor for SHH signaling in the neural tube. There are five distinct progenitor domains in the ventral neural tube: V3 interneurons , motor neurons (MN), V2 , V1 , and V0 interneurons (in ventral to dorsal order). These different progenitor domains are established by "communication" between different classes of homeobox transcription factors . (See Trigeminal Nerve .) These transcription factors respond to SHH gradient concentration. Depending upon
23798-406: The side of the body, which are reminiscent of a zebra's stripes, and which extend to the end of the caudal fin . Its shape is fusiform and laterally compressed, with its mouth directed upwards. The male is torpedo -shaped, with gold stripes between the blue stripes; the female has a larger, whitish belly and silver stripes instead of gold. Adult females exhibit a small genital papilla in front of
23961-414: The sides of the yolk (8 h panel) and begin forming a head and tail (16 h panel). The tail then grows and separates from the body (24 h panel). The yolk shrinks over time because the fish uses it for food as it matures during the first few days (72 h panel). After a few months, the adult fish reaches reproductive maturity (bottom panel). To encourage the fish to spawn, some researchers use a fish tank with
24124-467: The strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein. This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for
24287-461: The sugar ribose rather than deoxyribose . RNA also contains the base uracil in place of thymine . RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three- nucleotide sequences called codons , which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids . The genetic code
24450-809: The term gemmule to describe hypothetical particles that would mix during reproduction. Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries , Carl Correns , and Erich von Tschermak , who (claimed to have) reached similar conclusions in their own research. Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis , in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" ( Pangens in German), after Darwin's 1868 pangenesis theory. Twenty years later, in 1909, Wilhelm Johannsen introduced
24613-436: The term gene , he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen 's distinction between genotype (the genetic material of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment , the distinction between dominant and recessive traits,
24776-412: The term "gene" (inspired by the ancient Greek : γόνος, gonos , meaning offspring and procreation) and, in 1906, William Bateson , that of " genetics " while Eduard Strasburger , among others, still used the term "pangene" for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA)
24939-518: The ventral spinal cord. These incremental changes in vitro correspond to the distance of domains from the signaling tissue (notochord and floor plate) which subsequently differentiates into different neuronal subtypes as it occurs in vitro . Graded SHH signaling is suggested to be mediated through the Gli family of proteins, which are vertebrate homologues of the Drosophila zinc-finger -containing transcription factor Cubitus interruptus ( Ci ). Ci
25102-424: The wildtype). Sonic hedgehog may play a role in mammalian hair cell regeneration . By modulating retinoblastoma protein activity in rat cochlea, sonic hedgehog allows mature hair cells that normally cannot return to a proliferative state to divide and differentiate. Retinoblastoma proteins suppress cell growth by preventing cells from returning to the cell cycle , thereby preventing proliferation. Inhibiting
25265-460: The zebrafish reference genome revealed over 5 million single nucleotide variations and over 1.6 million insertion deletion variations. The zebrafish reference genome sequence of 1.4GB and over 26,000 protein coding genes was published by Kerstin Howe et al. in 2013. In October 2001, researchers from the University of Oklahoma published D. rerio's complete mitochondrial DNA sequence. Its length
25428-473: The zebrafish to gain new insights into the complexities of human musculoskeletal diseases, such as muscular dystrophy . Another focus of zebrafish research is to understand how a gene called Hedgehog , a biological signal that underlies a number of human cancers, controls cell growth. Inbred strains and traditional outbred stocks have not been developed for laboratory zebrafish, and the genetic variability of wild-type lines among institutions may contribute to
25591-447: Was first identified in the fruit fly Drosophila melanogaster in the classic Heidelberg screens of Christiane Nüsslein-Volhard and Eric Wieschaus , as published in 1980. These screens , which led to the researchers winning a Nobel Prize in 1995 along with developmental geneticist Edward B. Lewis , identified genes that control the segmentation pattern of the Drosophila embryos. The hh loss of function mutant phenotype causes
25754-450: Was first suggested by Gregor Mendel (1822–1884). From 1857 to 1864, in Brno , Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants , tracking distinct traits from parent to offspring. He described these mathematically as 2 combinations where n is the number of differing characteristics in the original peas. Although he did not use
25917-467: Was found in other teleosts , but not in tetrapods . This indicates that an evolutionary change in tetrapods may have led to humans relying on the U2AF2 protein for RNA splicing while these genes in zebrafish undergo splicing regardless of the presence of the protein. D. rerio has three transferrins , all of which cluster closely with other vertebrates . When close relatives mate, progeny may exhibit
26080-510: Was named after the video game character Sonic the Hedgehog . The gene was named by Robert Riddle, a postdoctoral fellow at the Tabin Lab , after his wife Betsy Wilder came home with a magazine containing an advert for the first game in the series, Sonic the Hedgehog (1991). In the zebrafish , two of the three vertebrate hh genes are duplicated: SHH a and SHH b (formerly described as tiggywinkle hedgehog , named for Mrs. Tiggy-Winkle ,
26243-435: Was only 12.3 °C (54.1 °F) and another unusually warm site was 38.6 °C (101.5 °F), but the zebrafish still appeared healthy. The unusually cold temperature was at one of the highest known zebrafish locations at 1,576 m (5,171 ft) above sea level, although the species has been recorded to 1,795 m (5,889 ft). The zebrafish is named for the five uniform, pigmented, horizontal, blue stripes on
26406-445: Was shown to be a complex genetic trait, rather than to follow a simple ZW or XY system. The zebrafish embryo develops rapidly, with precursors to all major organs appearing within 36 hours of fertilization. The embryo begins as a yolk with a single enormous cell on top (see image, 0 h panel), which divides into two (0.75 h panel) and continues dividing until there are thousands of small cells (3.25 h panel). The cells then migrate down
26569-430: Was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography , which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication. In
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