Item Type: | Article |
---|---|
Title: | Bcl11a (Ctip1) controls migration of cortical projection neurons through regulation of Sema3c |
Creators Name: | Wiegreffe, C., Simon, R., Peschkes, K., Kling, C., Strehle, M., Cheng, J., Srivatsa, S., Liu, P., Jenkins, N.A., Copeland, N.G., Tarabykin, V. and Britsch, S. |
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. 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. |
Keywords: | Basic Helix-Loop-Helix Transcription Factors, Carrier Proteins, Cell Differentiation, Cell Movement, Cell Polarity, Cerebral Cortex, Developmental Gene Expression Regulation, HEK293 Cells, Homeodomain Proteins, In Vitro Techniques, Mammalian Embryo, Microarray Analysis, Mutation, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Organ Culture Techniques, Semaphorins, Transcription Factors, Animals, Mice |
Source: | Neuron |
ISSN: | 0896-6273 |
Publisher: | Cell Press / Elsevier |
Volume: | 87 |
Number: | 2 |
Page Range: | 311-325 |
Date: | 15 July 2015 |
Official Publication: | https://doi.org/10.1016/j.neuron.2015.06.023 |
PubMed: | View item in PubMed |
Repository Staff Only: item control page