Neuron
Volume 87, Issue 2, 15 July 2015, Pages 311-325
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Article
Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c

https://doi.org/10.1016/j.neuron.2015.06.023Get rights and content
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Highlights

  • Bcl11a controls cell polarity and radial migration of upper layer cortical neurons

  • Sema3c is a major downstream effector of Bcl11a in migrating cortical neurons

  • Morphogenesis and survival of postmigratory upper layer neurons depend on Bcl11a

  • Deletion of Bcl11a in mice results in hypoplasia of superficial neocortex

Summary

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. In vivo 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.

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Present address: Institute of Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany