Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud

Citation
R. Merino et al., Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud, DEVELOP BIO, 206(1), 1999, pp. 33-45
Citations number
50
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENTAL BIOLOGY
ISSN journal
00121606 → ACNP
Volume
206
Issue
1
Year of publication
1999
Pages
33 - 45
Database
ISI
SICI code
0012-1606(19990201)206:1<33:EAFOGD>2.0.ZU;2-0
Abstract
Bone morphogenetic proteins (BMPs) constitute a large family of secreted si gnals involved in the formation of the skeleton but the specific function o f each member of this family remains elusive. GDF-5 is a member of the BMP family which has been implicated in several skeletogenic events including t he induction and growth of the appendicular cartilages, the determination o f joint forming regions, and the establishment of tendons. Here, we have st udied the function of GDF-5 in digit skeletogenesis by analyzing the effect s of its local administration in the developing autopod of embryonic chick and the regulation of its pattern of gene expression by other signals invol ved in digit morphogenesis. As reported in the mouse, the gdf-5 gene exhibi ts a precise distribution in the joint-forming regions of the developing ch icken digital rays. GDF-5 beads implanted at the tip of the digits promote intense cartilage growth and fail to induce morphological or molecular sign s of joint formation. Furthermore, GDF-5 beads implanted in the interdigits inhibit the formation of joints in the adjacent digits. These data suggest that the role of GDF-5 in joint formation is the control of growth and dif ferentiation of the cartilage of the epiphyseal regions of the phalanges ra ther than accounting for the differentiation of the sinovial joint tissues. The interdigital mesoderm in spite of its potential to form ectopic digits with their tendinous apparatus failed to form either ectopic cartilages or ectopic tendons after the implantation of GDF-5 beads in the stages preced ing cell death. At difference with other BMPs, GDF-5 exhibited only a weak cell death promoting effect. The BMP antagonist Noggin binds to GDF-5 and i s able to inhibit all the observed effects of this growth factor in vivo. P otential interactions of GDF-5 with other signals involved in digits morpho genesis were also explored. BMP-7 regulates negatively the expression of gd f-5 gene in the joint forming regions and local treatment with Noggin induc es the ectopic expression of gdf-5 in the interdigital mesoderm. Retroviral -induced misexpression of Indian or Sonic Hedgehog genes in the developing digits leads to the formation of digits without joints in which gdf-5 expre ssion occurs throughout the entire perichondrial surface. In conclusion, th is study indicates that GDF-5 is a signal regulated by other BMPs which con trols the growth and differentiation of the epiphyses of the digital cartil ages acting in close relationship with Hedgehog signaling. (C) 1999 Academi c Press.