Endothelin/endothelin-B receptor signals regulate ventricle-directed interkinetic nuclear migration of cerebral cortical neural progenitors

• Published in: Neurochemistry international 2011-02, Vol.58 (3), p.261-272
• Main Authors: Nishikawa, Kaori, Ayukawa, Koichi, Hara, Yoko, Wada, Keiji, Aoki, Shunsuke
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Movement - physiology; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Cells, Cultured; Cerebral cortex; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Endothelin; Endothelin B Receptor Antagonists; Endothelins - physiology; Fundamental and applied biological sciences. Psychology; G protein-coupled receptors; Interkinetic nuclear migration; Mice; Mice, Inbred C57BL; Neural progenitor cell; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Organ Culture Techniques; Receptor, Endothelin B - agonists; Receptor, Endothelin B - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2010.11.013

► ETB-R is the highest expression level among GPCRs expressed in NPCs. ► ETB-R is a critical regulator of INM that precedes neurogenesis. ► ETB-R is a dual function receptor promoting both motility and adhesion of NPCs. ► ETB-R-mediated assembly signals drive INM that precedes neurogenesis. 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 (ETB-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 ETB-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 ETB-R agonist, IRL-1620, accelerated interkinetic nuclear migration (INM) of NPCs toward the ventricular wall (VW) ex vivo. Conversely, a specific ETB-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 ETB-R-mediated assembly signals drive INM that precedes neurogenesis.