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Transcriptional Regulation of Cortical Neuron Migration by POU Domain Factors

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Science  22 Feb 2002:
Vol. 295, Issue 5559, pp. 1528-1532
DOI: 10.1126/science.1067132

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Abstract

The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, withBrn-1(/−)/Brn-2(/−) mice exhibiting cortical inversion.

  • * To whom correspondence should be addressed. E-mail: rmcevilly{at}ucsd.edu, mrosenfeld{at}ucsd.edu

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