کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4320908 | 1291552 | 2015 | 15 صفحه PDF | دانلود رایگان |
• 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
SummaryDuring 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.
Journal: - Volume 87, Issue 2, 15 July 2015, Pages 311–325