title: Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c.
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.
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiegreffe
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Peschkes
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Kling
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Strehle
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany.
authors.forename: Swathi
authors.initials: S
authors.lastname: Srivatsa
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
authors.forename: Pentao
authors.initials: P
authors.lastname: Liu
authors.affiliation: The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.affiliation: The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.affiliation: Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgerod, 23 Prospekt Gagarina (Gagarin Avenue), 603950 Nizhny Novgorod, Russia.
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: stefan.britsch@uni-ulm.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Britsch
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D012097:Repressor Proteins; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D039961:Semaphorins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C407733:Bcl11a protein, mouse; C110701:Neurod6 protein, mouse; C510203:semaphorin 3C protein, mouse