Achording to the zebrafish . . . a deficiency of chordin results in aberrant tail development (upper image).

A variety of growth and differentiation factors regulate the formation of the vertebrate skeleton by activating or repressing different transcription factors. Among the differentiation factors, members of the transforming growth factor-β (TGF-β) superfamily are implicated in both cartilage and bone-cell differentiation and in mediating the complex patterning of the skeleton. The bone morphogenetic proteins (BMPs), a small family of TGF-β–related proteins, stimulate mesenchymal cells to differentiate into chondrocytes and osteoblasts, which deposit the bone matrix and regulate the pattern of skeletal formation. Accordingly, inactivation or mutation of BMP genes causes skeletal malformations in mice, and some skeletal diseases in humans may also result from mutations or alterations in the levels or activities of BMPs.

Several secreted polypeptides, of which noggin and chordin are best characterized, regulate the extracellular activities of the BMPs. Their ability to associate with BMPs prevents them from binding to cell-surface receptors and thereby inhibits their effect on the cell. Last year, noggin was shown to inhibit BMP activity1 in skeletal morphogenesis. So, mice deficient in noggin have skeletal defects due to excessive cartilage formation and increased bone formation. Shannon Fisher and Marnie Halpern now provide evidence2 (see page 442) that skeletal development is regulated by chordin through its ability to block BMP activity. They show that zebrafish lacking chordin expression have aberrant levels of BMP proteins and abnormalities in fin and caudal skeletal patterning—which can be rescued by injections of chordin mRNA. In so doing, they underscore the advantages of using genetic screens of zebrafish to identify regulators of skeletal formation in vertebrates.