Embryonic Development of Bone and Regulation of Intramembranous and Endochondral Bone Formation

This chapter reviews the developmental biology of the skeleton. It describes the complex array of signals that influence each developmental stage. Skeletal cells are derived from three distinct embryonic cell lineages: neural crest cells contribute to the craniofacial skeleton; sclerotome cells from somites give rise to the axial skeleton; and lateral plate mesoderm cells from the appendicular component. The organization and morphology of the developing skeleton are established through a series of inductive interactions. The functional elements in these inductive and morphogenetic processes are not individual cells but rather interacting populations that elaborate an extensive extracellular matrix that, in turn, feeds back onto the matrix producing cells and controls their differentiation potential. Bone formation arising from a cartilaginous template is referred to as endochondral ossification. This is a complex, multistep process requiring the sequential formation and degradation of cartilaginous structures that serve as templates for the developing bones. In each phase of skeletal development, it is the appropriate interplay of a number of gene products that determines the final phenotypic outcome. Finally, this chapter explains a number of inherited disorders of the skeleton arising from mutant gene products that influence one of these specific phases. Knowledge of how specific gene defects contribute to bone pathophysiology is anticipated to guide future efforts in the treatment of inherited and metabolic skeletal disorders.