Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c

Christoph Wiegreffe, Ruth Simon, Katharina Peschkes, Carolin Kling, Michael Strehle, Jin Cheng, Swathi Srivatsa, Pentao Liu, Nancy A. Jenkins, Neal G. Copeland, Victor Tarabykin, Stefan Britsch

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

During neocortical development, neurons undergo polarization, oriented migration, and layer-type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here, we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons. Bcl11a-deficient late-born neurons fail to correctly switch from multipolar to bipolar morphology, resulting in impaired radial migration. We show that the expression of Sema3c is increased in migrating Bcl11a-deficient neurons and that Bcl11a is a direct negative regulator of Sema3c transcription. Invivo gain-of-function and rescue experiments demonstrate that Sema3c is a major downstream effector of Bcl11a required for the cell polarity switch and for the migration of upper layer neurons. Our data uncover a novel Bcl11a/. Sema3c-dependent regulatory pathway used by migrating cortical neurons. Wiegreffe etal. discover a novel Bcl11a/Sema3c-dependent regulatory pathway that controls polarization and radial migration of late-born upper layer cortical projection neurons. Deletion of Bcl11a in mice ultimately results in severe hypoplasia of upper neocortical layers.

Original languageEnglish (US)
Pages (from-to)311-325
Number of pages15
JournalNeuron
Volume87
Issue number2
DOIs
StatePublished - Jul 15 2015

ASJC Scopus subject areas

  • Neuroscience(all)

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