Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex
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...
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Elsevier B.V.
2015
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Online Access: | http://hdl.handle.net/1721.1/96093 https://orcid.org/0000-0003-1262-0592 |
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author | Buchman, Joshua J. Tseng, Huan-Chung Zhou, Ying Frank, Christopher Lee Xie, Zhigang Tsai, Li-Huei |
author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Buchman, Joshua J. Tseng, Huan-Chung Zhou, Ying Frank, Christopher Lee Xie, Zhigang Tsai, Li-Huei |
author_sort | Buchman, Joshua J. |
collection | MIT |
description | 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. |
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format | Article |
id | mit-1721.1/96093 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T14:10:19Z |
publishDate | 2015 |
publisher | Elsevier B.V. |
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spelling | mit-1721.1/960932022-09-28T18:59:26Z Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex Buchman, Joshua J. Tseng, Huan-Chung Zhou, Ying Frank, Christopher Lee Xie, Zhigang Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Buchman, Joshua J. Tseng, Huan-Chung Zhou, Ying Frank, Christopher Lee Tsai, Li-Huei 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. National Institutes of Health (U.S.) (grant NS37007) Howard Hughes Medical Institute (Investigator) 2015-03-19T19:48:14Z 2015-03-19T19:48:14Z 2010-05 Article http://purl.org/eprint/type/JournalArticle 08966273 http://hdl.handle.net/1721.1/96093 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. https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1016/j.neuron.2010.03.036 Neuron 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. application/pdf Elsevier B.V. Elsevier |
spellingShingle | Buchman, Joshua J. Tseng, Huan-Chung Zhou, Ying Frank, Christopher Lee Xie, Zhigang Tsai, Li-Huei Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title | Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title_full | Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title_fullStr | Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title_full_unstemmed | Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title_short | Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex |
title_sort | cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex |
url | http://hdl.handle.net/1721.1/96093 https://orcid.org/0000-0003-1262-0592 |
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