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.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Differentiation / genetics
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Cell Movement / genetics*
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Cell Polarity / genetics
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Cerebral Cortex / cytology*
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Cerebral Cortex / embryology*
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DNA-Binding Proteins
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Embryo, Mammalian
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Gene Expression Regulation, Developmental / genetics
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HEK293 Cells
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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In Vitro Techniques
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Mice
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Mice, Transgenic
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Microarray Analysis
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Neurons / physiology*
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Organ Culture Techniques
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Repressor Proteins
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Semaphorins / genetics
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Semaphorins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Bcl11a protein, mouse
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Carrier Proteins
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DNA-Binding Proteins
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Homeodomain Proteins
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Nerve Tissue Proteins
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Neurod6 protein, mouse
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Nuclear Proteins
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Repressor Proteins
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Semaphorins
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Transcription Factors
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empty spiracles homeobox proteins
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semaphorin 3C protein, mouse