Endothelin/endothelin-B receptor signals regulate ventricle-directed interkinetic nuclear migration of cerebral cortical neural progenitors |
| |
Authors: | Nishikawa Kaori Ayukawa Koichi Hara Yoko Wada Keiji Aoki Shunsuke |
| |
Institution: | Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. |
| |
Abstract: | We determined the expression profile of ~300 G protein-coupled receptors (GPCRs) in embryonic cortical neural progenitor cells (NPCs) and identified a number of highly expressed GPCRs, among which endothelin-B receptor (ET(B)-R) was expressed at the highest level. We also revealed that endothelins (ETs) were predominantly expressed in CD31-positive endothelial cells of the embryonic cerebral cortex. Activation of ET(B)-R induced NPC assembly in vitro by promoting fibronectin-dependent-motility and N-cadherin-associated cell contact. NPC assembly also required a Rho-family GTPase(s) and phosphatidylinositol-3-kinase. In the embryonic cerebral cortex, a specific ET(B)-R agonist, IRL-1620, accelerated interkinetic nuclear migration (INM) of NPCs toward the ventricular wall (VW) ex vivo. Conversely, a specific ET(B)-R antagonist, BQ788, slowed INM, thereby inducing mislocalization of phospho-histone H3-positive M-phase nuclei in the ventricular zone (VZ) and decreasing the number of Tuj1-positive newborn neurons. Our results suggest that ET(B)-R-mediated assembly signals drive INM that precedes neurogenesis. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|