G Alpha(S) Signaling In Skeletal Development, Homeostasis And Diseases

Skeletal development is exquisitely controlled both spatially and temporally by cell signaling networks. G alpha(s) is the stimulatory alpha-subunit in a heterotrimeric G protein complex transducing the signaling of G-protein-coupled receptors (GPCRs), responsible for controlling both skeletal development and homeostasis. G alpha(s), encoded by the GNAS gene in humans, plays critical roles in skeletal development and homeostasis by regulating commitment, differentiation and maturation of skeletal cells. G alpha(s)-mediated signaling interacts with the Wnt and Hedgehog signaling pathways, both crucial regulators of skeletal development, remodeling and injury repair. Genetic mutations that disrupt G alpha(s) functions cause human disorders with severe skeletal defects, such as fibrous dysplasia of bone and heterotopic bone formation. This chapter focuses on the crucial roles of G alpha(s) signaling during skeletal development and homeostasis, and the pathological mechanisms underlying skeletal diseases caused by GNAS mutations.