DEVELOPMENT AND DISEASE Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of secreted proteins, which also includes Cyr61, NOV, WISP1, WISP2 and WISP3 (Bork, 1993; Moussad and Brigstock, 2000; Perbal, 2001). CTGF is a major inducer of extracellular matrix (ECM) production in fibrotic diseases, which are characterized by excessive collagen deposition. CTGF is overexpressed in fibrotic lesions, and the degree of overexpression correlates with severity of disease (Blom et al., 2001; Dammeier et al., 1998; Frazier et al., 1996; Grotendorst, 1997; Lasky et al., 1998; Mori et al., 1999; Stratton et al., 2001). The ability of CTGF to induce collagen deposition in pathological conditions raises the possibility that it may be a mediator of ECM production in tissues such as cartilage and bone during development. However, nothing is known about its role in normal tissues. CTGF may act in part as a mediator of transforming growth factors β (TGFβs) and bone morphogenetic proteins (BMPs) during development. TGFβs play roles in a wide variety of developmental events, and TGFβ induces CTGF expression in many cell types because the CTGF promoter contains a TGFβ 2779 Development 130, 2779-2791 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00505