1. G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis
- Author
-
Ke Zhang, Huashun Li, Min Chen, Yang Hong, Lee S. Weinstein, Run Lei, Yanxia Wei, Hongchang Li, and Minyan Zhu
- Subjects
0301 basic medicine ,Embryology ,Physiology ,Cellular differentiation ,Cleft Lip and Palate ,lcsh:Medicine ,Mandible ,Ossification ,Adenylyl cyclase ,Gene Knockout Techniques ,Mice ,chemistry.chemical_compound ,Animal Cells ,GTP-Binding Protein alpha Subunits, Gs ,Morphogenesis ,Medicine and Health Sciences ,Maxilla ,lcsh:Science ,Musculoskeletal System ,Connective Tissue Cells ,Ganglia, Sympathetic ,Multidisciplinary ,Neural crest ,Cell Differentiation ,Anatomy ,Osteoblast Differentiation ,Cell biology ,Cleft Palate ,Neural Crest ,Connective Tissue ,Knockout mouse ,Bone Remodeling ,Cellular Types ,Spinal Nerve Roots ,Research Article ,Cell type ,Gs alpha subunit ,Biology ,Facial Bones ,03 medical and health sciences ,Chondrocytes ,Congenital Disorders ,Animals ,Birth Defects ,Craniofacial ,Protein kinase A ,Skeleton ,Mouth ,Skull ,Embryos ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Biological Tissue ,Cartilage ,030104 developmental biology ,Otorhinolaryngology ,chemistry ,Mutation ,lcsh:Q ,Physiological Processes ,Digestive System ,Developmental Biology - Abstract
The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.
- Published
- 2016