G Protein-Coupled Receptor Signaling through Gq and JNK Negatively Regulates Neural Progenitor Cell Migration

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-08, Vol.102 (35), p.12365-12370
• Main Authors: Mizuno, Norikazu, Kokubu, Hiroshi, Sato, Maiko, Nishimura, Akiyuki, Yamauchi, Junji, Kurose, Hitoshi, Itoh, Hiroshi, Kaziro, Yoshito
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animal migration behavior; Animals; Anthracenes - pharmacology; Biochemistry; Biological Sciences; Cell adhesion & migration; Cell Movement - drug effects; Cell Movement - physiology; Central nervous system; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Endothelin-1 - pharmacology; Enzyme Inhibitors - pharmacology; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Mice; Mice, Inbred ICR; Multipotent stem cells; Multipotent Stem Cells - cytology; Multipotent Stem Cells - drug effects; Multipotent Stem Cells - metabolism; Mutation; Nervous system; Neural stem cells; Neuroglia; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Progenitor cells; Proteins; Receptor, Endothelin B - metabolism; Receptors; Receptors, G-Protein-Coupled - metabolism; Signal Transduction; Stem cells; Tissue Culture Techniques
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0506101102

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 Gαq but not Gαi. The expression of constitutively active mutant of Gαq, GαqR183C, 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 Gαq 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.