Dataset Information

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.

SUBMITTER: Liu YH

PROVIDER: S-EPMC5343589 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.

Liu Yuan-Hsuan YH Tsai Jin-Wu JW Chen Jia-Long JL Yang Wan-Shan WS Chang Pei-Ching PC Cheng Pei-Lin PL Turner David L DL Yanagawa Yuchio Y Wang Tsu-Wei TW Yu Jenn-Yah JY

Scientific reports 20170309

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 ho ...[more]

PMID: 28276447

Similar Datasets

Project description:In rodent ventral telencephalon, diffusible morphogens induce expression of the proneural transcription factor ASCL1, which in turn induces expression of the transcription factor DLX2 that controls differentiation of cortical interneuron precursors and their tangential migration to the cerebral cortex. RNAseq analysis of human fetal samples of dorsal telencephalon revealed consistently high cortical expression of ASCL1 and increasing expression of DLX2 between 7.5 and 17 post-conceptional weeks (PCW). We explored whether cortical expression of these genes represented a population of intracortically derived interneuron precursors. Immunohistochemistry revealed an ASCL1+ /DLX2+ population of progenitor cells in the human ganglionic eminences between 6.5 and 12 PCW, but in the cortex there also existed a population of ASCL1+ /DLX2- progenitors in the subventricular zone (SVZ) that largely co-expressed cortical markers PAX6 or TBR2, although a few ASCL1+ /PAX6- progenitors were observed in the ventricular zone (VZ) and ASCL1+ cells expressing the interneuron marker GAD67 were present in the SVZ. Although rare in the VZ, DLX2+ cells progressively increased in number between 8 and 12 PCW across the cortical wall and the majority co-expressed LHX6 and originated either in the MGE, migrating to the lateral cortex, or from the septum, populating the medial wall. A minority co-expressed COUP-TFII, which identifies cells from the caudal ganglionic eminence (CGE). By 19 PCW, a significant increase in expression of DLX2 and ASCL1 was observed in the cortical VZ with a small proportion expressing both proteins. The DLX2+ cells did not co-express a cell division marker, so were not progenitors. The majority of DLX2+ cells throughout the cortical plate expressed COUP-TFII rather than LHX6+ . As the VZ declined as a proliferative zone it appeared to be re-defined as a migration pathway for COUP-TFII+ /DLX2+ interneurons from CGE to cortex. Therefore, in developing human cortex, ASCL1 expression predominantly marks a population of intermediate progenitors giving rise to glutamatergic neurons. DLX2 expression predominantly defines post-mitotic interneuron precursors.

Dataset Information

Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.

Publications

Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets