Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex
Name
Buchman-2010-Cdk5rap2 Interacts w.pdf
Size
4.28 MB
Format
Adobe PDF
Checksum (MD5)
0d72f1c06338442abffc0c56ec5bc323
Author(s)
Buchman, Joshua J.
Tseng, Huan-Chung
Zhou, Ying
Frank, Christopher Lee
Xie, Zhigang
Tsai, Li-Huei
Date Issued
May 2010
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.neuron.2010.03.036
