GENETIC ANALYSIS OF CCN GENE FUNCTION IN MAMMALIAN DEVELOPMENT

Gene expression patterns and numerous in vitro experiments suggest that CCNs may be required for multiple aspects of mammalian development. Roles for several CCN genes during mammalian development have been elucidated through genetic analysis in mice and humans. Mice lacking Ccn1 are characterized by insufficient placental vascularization and defective embryonic vasculature, confirming an essential and novel role for CCN1 in angiogenesis. Loss of Ccn2 in mice results in multiple defects in skeletal development, including impaired chondrocyte proliferation, decreased production of extracellular matrix components, and defective growth plate angiogenesis. Mutations in Ccn6 in humans are associated with defects in post-natal maintenance of articular cartilage. These genetic analyses have also shed light on signaling pathways utilized by CCNs and have revealed key molecular targets of CCN gene action.