Skeletal development: insights from targeting the mouse genome

Manipulation of the mouse genome through mis-expressing, knocking out, and introducing mutations into genes of interest has provided important insights into the genetic pathways responsible for human skeletal development. These pathways contribute to the sequential phases of skeletal morphogenesis that include patterning, condensation, and overt organogenesis of the membranous and endochondral embryonic skeletons and to subsequent linear growth. Disturbances in these pathways account for many developmental syndromes and disorders of the human skeleton. Recurrent themes include establishment of interlocking regulatory circuits involving growth factors, receptors, signalling pathways, and transcription factors that control cellular programmes such as migration, adhesion, proliferation, differentiation, and apoptosis, and use of common molecules for different purposes. Technical advances suggest that genetic engineering in mice will continue to be highly instructive in the field of skeletal biology.