The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb

Citation
R. Merino et al., The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb, DEVELOPMENT, 126(23), 1999, pp. 5515-5522
Citations number
44
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENT
ISSN journal
09501991 → ACNP
Volume
126
Issue
23
Year of publication
1999
Pages
5515 - 5522
Database
ISI
SICI code
0950-1991(199912)126:23<5515:TBAGRO>2.0.ZU;2-A
Abstract
In this study, we have analyzed the expression and function of Gremlin in t he developing avian limb, Gremlin is a member of the DAN family of BMP anta gonists highly conserved through evolution able to bind and block BMP2, BMP 4 and BMP7. At early stages of development, gremlin is expressed in the dor sal and ventral mesoderm in a pattern complementary to that of bmp2, bmp4 a nd bmp7, The maintenance of gremlin expression at these stages is under the control of the AER, ZPA, and BMPs. Exogenous administration of recombinant Gremlin indicates that this protein is involved in the control of limb out growth, This function appears to be mediated by the neutralization of BMP f unction to maintain an active AER, to restrict the extension of the areas o f programmed cell death and to confine chondrogenesis to the central core m esenchyme of the bud. At the stages of digit formation, gremlin is expresse d in the proximal boundary of the interdigital mesoderm of the chick autopo d, The anti-apoptotic influence of exogenous Gremlin, which results in the formation of soft tissue syndactyly in the chick, together with the express ion of gremlin in the duck interdigital webs, indicates that Gremlin regula tes the regression of the interdigital tissue. At later stages of limb deve lopment, gremlin is expressed in association with the differentiating skele tal pieces, muscles and the feather buds. The different expression of Greml in in relation with other BMP antagonists present in the limb bud, such as Noggin, Chordin and Follistatin indicates that the functions of BMPs are re gulated specifically by the different BMP antagonists, acting in a compleme ntary fashion rather than being redundant signals.