TY - JOUR
T1 - Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c
AU - Wiegreffe, Christoph
AU - Simon, Ruth
AU - Peschkes, Katharina
AU - Kling, Carolin
AU - Strehle, Michael
AU - Cheng, Jin
AU - Srivatsa, Swathi
AU - Liu, Pentao
AU - Jenkins, Nancy A.
AU - Copeland, Neal G.
AU - Tarabykin, Victor
AU - Britsch, Stefan
PY - 2015/7/15
Y1 - 2015/7/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2015.06.023
DO - 10.1016/j.neuron.2015.06.023
M3 - Article
C2 - 26182416
AN - SCOPUS:84937395526
VL - 87
SP - 311
EP - 325
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -