Cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex.
Neuron
; 66(3): 386-402, 2010 May 13.
Article
em En
| MEDLINE
| ID: mdl-20471352
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neocórtex
/
Peptídeos e Proteínas de Sinalização Intracelular
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Neurogênese
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Antígenos
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Proteínas do Tecido Nervoso
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article