Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Institute of Brain Science, National Yang-Ming University, Taipei 112, Taiwan.
Sci Rep. 2017 Mar 9;7:42895. doi: 10.1038/srep42895.
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.
在发育过程中，来自腹侧端脑的皮质中间神经元经切线迁移到背侧端脑。虽然 Achaete-scute 家族 bHLH 转录因子 1（Ascl1）在发育中的端脑中发挥重要作用，但 Ascl1 是否调节切线迁移尚不清楚。在这里，我们发现 Ascl1 促进了背侧端脑脑室区/脑室下区（VZ/SVZ）和中间区（IZ）的切线迁移。远端同源盒 2（Dlx2）在促进 VZ/SVZ 上的切线迁移方面作为 Ascl1 的下游因子起作用，但在 IZ 上不起作用。我们进一步鉴定 Eph 受体 B2（Ephb2）为 Ascl1 的直接靶标。EphB2 的敲低破坏了 VZ/SVZ 和 IZ 迁移途径的分离。EphB2 的配体 Ephrin-A5，足以排斥体外表达 Ascl1 的细胞和体内切线迁移的皮质中间神经元。总之，我们的结果表明，Ascl1 诱导 Dlx2 和 Ephb2 的表达，以维持背侧端脑中不同的切线迁移途径。
