Neural tube defects and impaired neural progenitor cell proliferation in Gbeta1-deficient mice.
Heterotrimeric G proteins are well known for their roles in signal transduction downstream of G protein-coupled receptors (GPCRs), and both Galpha subunits and tightly associated Gbetagamma subunits regulate downstream effector molecules. Compared to Galpha subunits, the physiological roles of individual Gbeta and Ggamma subunits are poorly understood. In this study, we generated mice deficient in the Gbeta1 gene and found that Gbeta1 is required for neural tube closure, neural progenitor cell proliferation, and neonatal development. About 40% Gbeta1(-/-) embryos developed neural tube defects (NTDs) and abnormal actin organization was observed in the basal side of neuroepithelium. In addition, Gbeta1(-/-) embryos without NTDs showed microencephaly and died within 2 days after birth. GPCR agonist-induced ERK phosphorylation, cell proliferation, and cell spreading, which were all found to be regulated by Galphai and Gbetagamma signaling, were abnormal in Gbeta1(-/-) neural progenitor cells. These data indicate that Gbeta1 is required for normal embryonic neurogenesis.
Okae
Hiroaki
H
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Iwakura
Yoichiro
Y
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian; D019332:Endothelin-1 / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits; D018507:Gene Expression Regulation, Developmental; D020962:Heterotrimeric GTP-Binding Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D009436:Neural Tube Defects / Q000235:genetics* / Q000503:physiopathology; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D019332:Endothelin-1; D044387:GTP-Binding Protein beta Subunits; C491082:Gnb1 protein, mouse; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D020962:Heterotrimeric GTP-Binding Proteins; D013110:Sphingosine; C032881:lysophosphatidic acid