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47-554: ASPM may refer to: ASPM (gene) , a human gene Active State Power Management , a computer power management protocol Aviation System Performance Metrics , an FAA database of the National Airspace System See also [ edit ] Aspirant de marine , a French Canadian subordinate officer Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with
94-454: A nonsense mutation (L3080X), a deletion of seven nucleotides (1260delTCAAGTC), and a missense mutation (Q3180P). Gul et al. found that parents who were heterozygous carriers for ASPM had normal cerebral circumferences and normal intelligence levels. The scientists were unable to identify mutations at the MCPH5 locus in nine families who had members affected by MCPH. They concluded that
141-646: A mutation in humans is linked to severe cases of microcephaly. With a loss of function in Aspm , ferrets with Aspm mutations saw a 40% decrease in overall brain size coupled with no reduction in body size, similar to the effects of loss of ASPM in humans. The study also looked at the neurodevelopmental pathways and mechanisms leading to neurogenesis in the KO ferrets compared to the WT controls, specifically studying three different neuron progenitor cell ( NPC ) types, all of which express
188-499: A role in neural differentiation . When looking at adult brains in Aspm KO mice, there was a trend in overall size reduction, and variations in cortical thickness between mutant and wild type models. In the somatosensory cortex, KO mice had a significantly thicker layer I cortex, thinner layer VI cortex, and an overall decrease in cortical thickness in the cortical plate . Certain transcription factors expressions were also abnormal in
235-623: A role of the expressed Aspm gene product in mitotic spindle regulation. The function is conserved, the C. elegans protein ASPM-1 was shown to be localized to spindle asters, where it regulates spindle organization and rotation by interacting with calmodulin, dynein and NuMA-related LIN-5. One mouse study looking at medulloblastoma growth in mice to study the Aspm gene, an ortholog to human ASPM, suggests that Aspm expression may drive postnatal cerebellar neurogenesis . This process occurs late in embryogenesis and immediately after birth over
282-782: A selective sweep in the Chinese . The SV2B gene, which encodes a synaptic vesicle protein, likewise shows evidence of a selective sweep in African-Americans . Neurogenesis Neurogenesis is the process by which nervous system cells, the neurons , are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans . Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes , and subgranular zone radial astrocytes , among others. Neurogenesis
329-492: A time span of about 2 weeks in mice and 12 months in humans, and is regulated by the expression of the Shh gene. In proliferating cerebellar granule neuron progenitors ( CGNPs ), Shh expression in mouse models showed four times the amount of Aspm expression than those deprived of Shh expression in-vivo . This induction of Aspm and up-regulation during cerebellar neurogenesis was also seen in real-time PCR , where its expression
376-511: Is a protein that in humans is encoded by the ASPM gene . ASPM is located on chromosome 1 , band q31 (1q31). The ASPM gene contains 28 exons and codes for a 3477 amino-acid-long protein. The ASPM protein is conserved across species including human, mouse, Drosophila , and C. elegans . Defective forms of the ASPM gene are associated with autosomal recessive primary microcephaly . "ASPM"
423-440: Is also found with an unusually high percentage among the people of Papua New Guinea , with a 59.4% occurrence. The mean estimated age of the ASPM allele of 5,800 years ago roughly correlates with the development of written language, spread of agriculture and development of cities. Currently, two alleles of this gene exist: the older (pre-5,800 years ago) and the newer (post-5,800 years ago). About 10% of humans have two copies of
470-496: Is an acronym for " A bnormal Sp indle-like, M icrocephaly-associated", which reflects its being an ortholog to the Drosophila melanogaster "abnormal spindle" ( asp ) gene. The expressed protein product of the asp gene is essential for normal mitotic spindle function in embryonic neuroblasts and regulation of neurogenesis. A new allele of ASPM arose sometime in the past 14,000 years (mean estimate 5,800 years), during
517-547: Is characterized by a smaller cerebral cortex associated with mild to moderate mental retardation and no other neurological deficits. Additionally, MCPH is associated with the absence of environmental causes such as intrauterine infections, exposure to prenatal radiation or drugs, maternal phenylketonuria, and birth asphyxia. MCPH has an incidence rate of 1/30,000 to 1/250,000 in western populations. To date, mutations in six loci and four genes associated with microcephaly have been discovered in humans. ASPM , one of these genes,
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#1732793469352564-420: Is debated. The hippocampus plays a crucial role in the formation of new declarative memories, and it has been theorized that the reason human infants cannot form declarative memories is because they are still undergoing extensive neurogenesis in the hippocampus and their memory-generating circuits are immature. Many environmental factors, such as exercise, stress, and antidepressants have been reported to change
611-420: Is derived from the neural tube , which contains NSCs that will later generate neurons . However, neurogenesis doesn't begin until a sufficient population of NSCs has been achieved. These early stem cells are called neuroepithelial cells (NEC)s, but soon take on a highly elongated radial morphology and are then known as radial glial cells (RGC)s. RGCs are the primary stem cells of the mammalian CNS, and reside in
658-522: Is found at the MCPH5 locus. The most common cause of MCPH in humans is homozygous genetic mutation of the ASPM gene , orthologous to the Drosophila abnormal spindle gene ( asp ). In humans, the ASPM gene may play a strong role in the growth of the cerebral cortex . A total of 22 mutations have been discovered in the ASPM gene in individuals from Pakistan, Turkey, Yemen, Saudi Arabia, Jordan, and
705-464: Is most active during embryonic development and is responsible for producing all the various types of neurons of the organism, but it continues throughout adult life in a variety of organisms. Once born, neurons do not divide (see mitosis ), and many will live the lifespan of the animal, except under extraordinary and usually pathogenic circumstances. During embryonic development, the mammalian central nervous system (CNS; brain and spinal cord )
752-591: Is most likely a non-functioning protein also seen in truncating point mutations reported in MCPH patients. A new allele (version) of ASPM appeared sometime within the last 14,100 years, with a mean estimate of 5,800 years ago. The new allele has a frequency of about 50% in populations of the Middle East and Europe, it is less frequent in East Asia, and has low frequencies among Sub-Saharan African populations. It
799-430: Is seen in germline abnormalities within mouse models. Mutations in Aspm were shown to reduce fertility in both female and male mice, indicated by a decrease in the rate of pregnancy and consequently the number of offspring, as well as a decrease in female ovarian size, as well as male sperm count and testicular size. The focus on severe germline mutations (as opposed to only mild microcephaly) in these mouse models raises
846-482: Is somehow advantageous to the individual. Testing the IQ of those with and without new ASPM allele has shown no difference in average IQ, providing no evidence to support the notion that the gene increases intelligence. Other genes related to brain development appear to have come under selective pressure in different populations. The DAB1 gene, involved in organizing cell layers in the cerebral cortex, shows evidence of
893-510: The ASPM gene. Genotyping using microsatellite regions in the gene revealed that MCPH5 locus mutations were the most common cause of MCPH. Genotyping further linked mutations in the MCPH2 locus, MCPH4 locus, and the MCPH6 locus to microcephaly. Sequence analysis of ASPM in humans revealed four novel mutations; these four types of mutations are an insertion of four nucleotides (9118insCATT),
940-536: The Holocene , it seems to have swept through much of the European and Middle-Eastern population. Although the new allele is evidently beneficial, researchers do not know what it does. The mouse gene, Aspm , is expressed in the primary sites of prenatal cerebral cortical neurogenesis . The difference between Aspm and ASPM is a single, large insertion coding for so-called IQ domains . Studies in mice also suggest
987-455: The "RP11-32D17" insert and used Fluorescence in situ Hybridization (FISH) in order to label the clones with fluorescein-12-dUTP. In order to precisely locate the translocation breakpoint, the Bam HI digestion fragments of "RP11-32D17" were analyzed. The translocation breakpoint was located to be within intron 17 of the ASPM gene. The translocation resulted in a truncated ASPM protein, which
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#17327934693521034-462: The KO mice. For example, Tbr1 and Satb2 had an increased presence in the cortical sub-plate, the first of which is important for differentiation and neuronal migration, and the second of which is a regulator of transcription and chromosomal remodeling. While mouse studies have established the role of Aspm mutations in microcephaly, several have linked this mutation to other significant defects. One study showed nerve fiber impairments in which
1081-530: The Netherlands. A study completed in Karnataka, South India by Kumar et al. analyzed the genetics of MCPH due to mutations in the ASPM gene. The study included nine families with blood relatives across many familial generations. Kumar et al. performed High-resolution G-banding chromosome analysis and haplotype analysis of individuals and families of those affected by MCPH. Kumar et al. found that
1128-524: The SVZ of the striatum to the olfactory bulb through the rostral migratory stream (RMS). The migrating neuroblasts in the olfactory bulb become interneurons that help the brain communicate with these sensory cells. The majority of those interneurons are inhibitory granule cells , but a small number are periglomerular cells . In the adult SVZ, the primary neural stem cells are SVZ astrocytes rather than RGCs. Most of these adult neural stem cells lie dormant in
1175-814: The South Indian families affected by mutations in the MCPH5 locus did not share a common disease haplotype; thus the authors proposed that different mutations in the ASPM gene are responsible for MCPH. A similar genetic study of MCPH in Pakistani families was done by Gul et al. in order to evaluate the relationship between ASPM gene mutations and microcephaly. The study was approved by the Institutional Review Board of Quaid-I-Azam University in Islamabad, Pakistan, and involved extraction of DNA and PCR techniques in order to genetically map
1222-406: The adult, but in response to certain signals, these dormant cells, or B cells, go through a series of stages, first producing proliferating cells, or C cells. The C cells then produce neuroblasts , or A cells, that will become neurons. Significant neurogenesis also occurs during adulthood in the hippocampus of many mammals, from rodents to some primates , although its existence in adult humans
1269-525: The already neurogenic niches. There is evidence that new neurons are produced in the dentate gyrus of the adult mammalian hippocampus, the brain region important for learning, motivation, memory, and emotion. A study reported that newly made cells in the adult mouse hippocampus can display passive membrane properties, action potentials and synaptic inputs similar to the ones found in mature dentate granule cells. These findings suggested that these newly made cells can mature into more practical and useful neurons in
1316-434: The analogous mutation in mice only results in mild brain size reduction. Ferrets also show more similarities to humans in terms of brain structure; ferrets' brains have gyrification in high amounts similar to humans, different from the relatively smooth brains of mice. As a result, there is less cortical surface area in mice compared to that of ferrets and humans. In this 2018 study, researchers targeted Aspm exon 15, where
1363-404: The ayahuasca infusion promotes neurogenesis on the subgranular zone of the dentate gyrus in the hippocampus. A study showed that a low dose (0.1 mg/kg) of psilocybin given to mice increased neurogenesis in the hippocampus 2 weeks after administration, while a high dose (1 mg/kg) significantly decreased neurogenesis. No orally-available drugs are known to elicit neurogenesis outside of
1410-482: The central nervous system arise from three types of neural stem and progenitor cells: neuroepithelial cells, radial glial cells and basal progenitors, which go through three main divisions: symmetric proliferative division; asymmetric neurogenic division; and symmetric neurogenic division. Out of all the three cell types, neuroepithelial cells that pass through neurogenic divisions have a much more extended cell cycle than those that go through proliferative divisions, such as
1457-491: The developing and adult mammalian brain. DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs) . Methylcytosine demethylation is catalyzed in several stages by TET enzymes that carry out oxidative reactions (e.g. 5-methylcytosine to 5-hydroxymethylcytosine ) and enzymes of the DNA base excision repair (BER) pathway. Neurogenesis can be a complex process in some mammals. In rodents for example, neurons in
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1504-550: The embryonic ventricular zone , which lies adjacent to the central fluid-filled cavity ( ventricular system ) of the neural tube . Following RGC proliferation, neurogenesis involves a final cell division of the parent RGC, which produces one of two possible outcomes. First, this may generate a subclass of neuronal progenitors called intermediate neuronal precursors (INP)s, which will divide one or more times to produce neurons. Alternatively, daughter neurons may be produced directly. Neurons do not immediately form neural circuits through
1551-497: The growth of axons and dendrites. Instead, newborn neurons must first migrate long distances to their final destinations, maturing and finally generating neural circuitry. For example, neurons born in the ventricular zone migrate radially to the cortical plate , which is where neurons accumulate to form the cerebral cortex . Thus, the generation of neurons occurs in a specific tissue compartment or 'neurogenic niche' occupied by their parent stem cells. The rate of neurogenesis and
1598-558: The mammalian brain unfolds, neural progenitor and stem cells switch from proliferative divisions to differentiative divisions . This progression leads to the generation of neurons and glia that populate cortical layers . Epigenetic modifications play a key role in regulating gene expression in the cellular differentiation of neural stem cells . Epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation . These modifications are critical for cell fate determination in
1645-543: The medulla cortex region of their optic lobes. These organisms can represent a model for the genetic analysis of adult neurogenesis and brain regeneration. There has been research that discuss how the study of “damage-responsive progenitor cells” in Drosophila can help to identify regenerative neurogenesis and how to find new ways to increase brain rebuilding. Recently, a study was made to show how “low-level adult neurogenesis” has been identified in Drosophila, specifically in
1692-463: The medulla cortex region, in which neural precursors could increase the production of new neurons, making neurogenesis occur. In Drosophila, Notch signaling was first described, controlling a cell-to-cell signaling process called lateral inhibition , in which neurons are selectively generated from epithelial cells . In some vertebrates, regenerative neurogenesis has also been shown to occur. An in vitro and in vivo study found that DMT present in
1739-411: The mitotic marker Ki-67 and undergo radial glial migration to the cortical plate. They found that outer subventricular zone ( OSVZ ) NPCs were largely displaced, especially frontally and dorsally which mirrors the effects seen in cortical volume reductions due to ASPM KO. Human primary microcephaly (MCPH) is a distinct subtype that is genetically inherited as an autosomal recessive trait. MCPH
1786-430: The mutations could be located in the regulatory sequences of ASPM , or that a gene other than ASPM located in the same region could be mutated. The types of mutations causing MCPH in humans was expanded by a study done by Pichon et al. on an individual with primary microcephaly, as the study revealed a translocation breakpoint in the ASPM gene. Pichon et al. obtained BAC clones with Bam HI digestion fragments of
1833-593: The neurons of the CNS varies widely across mammals, and brain neurogenesis is not always complete by the time of birth. For example, mice undergo cortical neurogenesis from about embryonic day (post-conceptional day) (E)11 to E17, and are born at about E19.5. Ferrets are born at E42, although their period of cortical neurogenesis does not end until a few days after birth. In contrast, neurogenesis in humans generally begins around gestational week (GW) 10 and ends around GW 25 with birth about GW 38–40. As embryonic development of
1880-411: The new ASPM allele, while about 50% have two copies of the old allele. The other 40% of humans have one copy of each. Of those with an instance of the new allele, 50% of them are an identical copy. The allele affects genotype over a large (62 kbp) region, a so called selective sweep which signals a rapid spread of a mutation (such as the new ASPM) through the population; this indicates that the mutation
1927-532: The question as to whether or not human ASPM selection may be more significantly linked to reproduction than brain size. In addition to mouse models, a study using ferrets reveals more about ASPM and its role in determining cortical size and thickness. The researchers from this study chose ferrets over mouse models due to incongruencies between Aspm effects in mice versus ASPM effects in humans - humans with microcephaly due to this gene mutation tend to have significantly reduced brain sizes (about 50% reduction), whereas
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1974-496: The radial glial cells and basal progenitors. In the human, adult neurogenesis has been shown to occur at low levels compared with development, and in only three regions of the brain: the adult subventricular zone (SVZ) of the lateral ventricles , the amygdala and the dentate gyrus of the hippocampus . In many mammals, including rodents, the olfactory bulb is a brain region containing cells that detect smell , featuring integration of adult-born neurons, which migrate from
2021-404: The rate of neurogenesis within the hippocampus of rodents. Some evidence indicates postnatal neurogenesis in the human hippocampus decreases sharply in newborns for the first year or two after birth, dropping to "undetectable levels in adults." Neurogenesis has been best characterized in model organisms such as the fruit fly Drosophila melanogaster . Neurogenesis in these organisms occur in
2068-461: The shape and form of cortex and white matter tissue was altered. This was shown postnatally comparing KO mice and controls, where both cell number and cortical thickness was decreased in KO mice. Using a cell staining methodology for histological analysis, the study also showed shorter distances between adjacent neurons in KO mice, indicating abnormalities in cell alignment in the absence of normal Aspm . Another significant impact of mutated Aspm
2115-746: The title ASPM . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=ASPM&oldid=756729489 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages ASPM (gene) 259266 12316 ENSG00000066279 ENSMUSG00000033952 Q8IZT6 Q8CJ27 NM_018136 NM_001206846 NM_009791 NP_001193775 NP_060606 NP_033921 Abnormal spindle-like microcephaly-associated protein , also known as abnormal spindle protein homolog or Asp homolog ,
2162-515: The type of neuron generated (broadly, excitatory or inhibitory) are principally determined by molecular and genetic factors. These factors notably include the Notch signaling pathway , and many genes have been linked to Notch pathway regulation . The genes and mechanisms involved in regulating neurogenesis are the subject of intensive research in academic, pharmaceutical , and government settings worldwide. The amount of time required to generate all
2209-425: Was relatively high at the peak of neurogenesis and much lower at the end of neurogenesis. Additionally, the study indicates that Aspm is necessary for cerebellar neurogenesis. In the presence of Aspm KO mutations and deletions, experimental mice models show decreased cerebellar volume under MRI , compared to the controls. In addition to mutated Aspm 's effects on neurogenesis, these mutations may also play
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