Cenpj/CPAP Regulates Progenitor Divisions and Neuronal Migration in the Cerebral Cortex Downstream of Ascl1

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Mar 11

PMID 25753651

Citations 24

Authors

Patricia P Garcez

Javier Diaz-Alonso

Ivan Crespo-Enriquez

Diogo Castro

Donald Bell

Francois Guillemot

Affiliations

Soon will be listed here.

Abstract

The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that Cenpj, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of Cenpj during cortical development by in utero electroporation knockdown and found that silencing Cenpj in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of Cenpj in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that Cenpj mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in Cenpj.

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