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.
Highlights
Neural crest cells (NCCs) are transient population of multipotent progenitors which arise from the border between neural plate and epidermis
These results indicate that loss of Gsα in NCCs leads to craniofacial malformations, defective development of dorsal root ganglion (DRG) and sympathetic ganglia
In Wnt1-cre;Gsαf/f mutants, the phosphorylation of cAMP response element binding protein (CREB) (P-CREB), and the phosphorylation of smad2 and smad5 (P-Smad2 and P-Smad5), were down-regulated (Fig 6D). These results suggest that loss of Gsα in NCCs leads to impaired CREB and bone morphogenetic protein (BMP) signaling
Summary
Neural crest cells (NCCs) are transient population of multipotent progenitors which arise from the border between neural plate and epidermis. NCCs undergo an epithelium to mesenchyme transition (EMT) process, migrate stereotypically to different locations, differentiate into multiple cell types [1,2,3,4,5,6,7]. Cranial NCCs, which originate from posterior forebrain and posterior hindbrain, contribute to bones, cartilages, connective tissues and cranial ganglia in face and neck. Cardiac NCCs, a subpopulation of cranial NCCs emanating from rhombomeres 6–8, give rise to parts of cardiac septum, thyroid and thymus. Trunk NCCs arising from caudal to the fourth somite are necessary for the formation of enteric.
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