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Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex

Author(s)
Buchman, Joshua J.; Tseng, Huan-Chung; Zhou, Ying; Frank, Christopher Lee; Xie, Zhigang; Tsai, Li-Huei; ... Show more Show less
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Abstract
Primary autosomal-recessive microcephaly (MCPH) and Majewski osteodysplastic primordial dwarfism type II (MOPDII) are both genetic diseases that result in decreased brain size at birth. MCPH is thought to arise from alterations in the size of the neural progenitor pool, but the cause of this defect has not been thoroughly explored. We find that one of the genes associated with MCPH, Cdk5rap2, is highly expressed in the neural progenitor pool and that its loss results in a depletion of apical progenitors and increased cell-cycle exit leading to premature neuronal differentiation. We link Cdk5rap2 function to the pericentriolar material protein pericentrin, loss of function of which is associated with MOPDII. Depletion of pericentrin in neural progenitors phenocopies effects of Cdk5rap2 knockdown and results in decreased recruitment of Cdk5rap2 to the centrosome. Our findings uncover a common mechanism, involving aberrations in the neurogenesis program, that may underlie the development of microcephaly in multiple diseases.
Date issued
2010-05
URI
http://hdl.handle.net/1721.1/96093
Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Journal
Neuron
Publisher
Elsevier B.V.
Citation
Buchman, Joshua J., Huan-Chung Tseng, Ying Zhou, Christopher L. Frank, Zhigang Xie, and Li-Huei Tsai. “Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex.” Neuron 66, no. 3 (May 2010): 386–402. © 2010 Elsevier Inc.
Version: Final published version
ISSN
08966273

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