title: G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration.
abstract: In the early development of the central nervous system, neural progenitor cells divide in an asymmetric manner and migrate along the radial glia cells. The radial migration is an important process for the proper lamination of the cerebral cortex. Recently, a new mode of the radial migration was found at the intermediate zone where the neural progenitor cells become multipolar and reduce the migration rate. However, the regulatory signals for the radial migration are unknown. Using the migration assay in vitro, we examined how neural progenitor cell migration is regulated. Neural progenitor cells derived from embryonic mouse telencephalon migrated on laminin-coated dishes. Endothelin (ET)-1 inhibited the neural progenitor cell migration. This ET-1 effect was blocked by BQ788, a specific inhibitor of the ETB receptor, and by the expression of a carboxyl-terminal peptide of Galpha q but not Galpha i. The expression of constitutively active mutant of Galpha q, Galpha qR183C, inhibited the migration of neural progenitor cells. Moreover, the inhibitory effect of ET-1 was suppressed by the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the expression of the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of the JNK pathway. Using the slice culture system of embryonic brain, we demonstrated that ET-1 and the constitutively active mutant of Galpha q caused the retention of the neural progenitor cells in the intermediate zone and JNK-binding domain of JNK-interacting protein-1 abrogated the effect of ET-1. These results indicated that G protein-coupled receptor signaling negatively regulates neural progenitor cell migration through Gq and JNK.
authors.affiliation: Department of Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kokubu
authors.forename: Maiko
authors.initials: M
authors.lastname: Sato
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Nishimura
authors.forename: Junji
authors.initials: J
authors.lastname: Yamauchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: D000873:Anthracenes; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D044023:Receptor, Endothelin B; D043562:Receptors, G-Protein-Coupled; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11