Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c
2015; Cell Press; Volume: 87; Issue: 2 Linguagem: Inglês
10.1016/j.neuron.2015.06.023
ISSN1097-4199
AutoresChristoph Wiegreffe, Ruth Simon, Katharina Peschkes, Carolin Kling, Michael Strehle, Jin Cheng, Swathi Srivatsa, Pentao Liu, Nancy A. Jenkins, N G Copeland, Victor Tarabykin, Stefan Britsch,
Tópico(s)Developmental Biology and Gene Regulation
ResumoDuring 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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