The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors
Open accessAbstract
Microcephaly affects ∼1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures. We analyzed the mechanisms underlying brain size determination in a mouse model of human microcephaly. The Hertwig's anemia (an) mutant shows peripheral blood cytopenias, spontaneous aneuploidy and a predisposition to hematopoietic tumors. We found that the an mutation is a genomic inversion of exon 4 of Cdk5rap2, resulting in an in-frame deletion of exon 4 from the mRNA. The finding that CDK5RAP2 human mutations cause microcephaly prompted further analysis of Cdk5rap2an/an mice and we demonstrated that these mice exhibit microcephaly comparable to that of the human disease, resulting from striking neurogenic defects that include proliferative and survival defects in neuronal progenitors. Cdk5rap2an/an neuronal precursors exit the cell cycle prematurely and many undergo apoptosis. These defects are associated with impaired mitotic progression coupled with abnormal mitotic spindle pole number and mitotic orientation. Our findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation.
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Metadata
- Authors
- Lizarraga, S. B., Margossian, S. P., Harris, M. H., Campagna, D. R., Han, A.-P., Blevins, S., Mudbhary, R., Barker, J. E., Walsh, C. A., & Fleming, M. D.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2010-06-01
- Volume
- 137
- Issue
- 11
- Pages
- 1907-1917
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2019695320
- Cited by
- 273
- References
- 58
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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