title: Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.
abstract: During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ. We further identified Eph receptor B2 (Ephb2) as a direct target of Ascl1. Knockdown of EphB2 disrupted the separation of the VZ/SVZ and IZ migratory routes. Ephrin-A5, a ligand of EphB2, was sufficient to repel both Ascl1-expressing cells in vitro and tangentially migrating cortical interneurons in vivo. Together, our results demonstrate that Ascl1 induces expression of Dlx2 and Ephb2 to maintain distinct tangential migratory routes in the dorsal telencephalon.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yuan-Hsuan
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei 112, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Jin-Wu
authors.initials: JW
authors.lastname: Tsai
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Wan-Shan
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Chang
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Cheng
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Turner
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Tsu-Wei
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Jenn-Yah
authors.initials: JY
authors.lastname: Yu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D051381:Rats; D036183:Receptor, EphB2 / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D036183:Receptor, EphB2; D014157:Transcription Factors; C499318:Ascl1 protein, rat; C088334:Distal-less homeobox proteins; C000628988:Ephb2 protein, rat