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

Development (Cambridge) - Tập 126 Số 23 - Trang 5515-5522 - 1999
Ramón Merino1, Joaquín Rodríguez‐León2, D. Macías2, Y. Gañán2, Aris N. Economides3, Juan M. Hurlé4
1Hospital Universitario Marques de Valdecilla 1 Unidad de Investigación , , Santander 39008, Spain
2Universidad de Extremadura 2 Departamento de Ciencias Morfológicas y Biología Animal y Celular ,. , Badajoz 06071, Spain
33 Regeneron Pharmaceuticals, Inc. Tarrytown, NY 10591-6707, USA
4Facultad de Medicina,. Universidad de Cantabria 4 Departamento de Anatomía y Biología Celular , , Santander 39011, Spain

Tóm tắt

Abstract In this study, we have analyzed the expression and function of Gremlin in the developing avian limb. Gremlin is a member of the DAN family of BMP antagonists highly conserved through evolution able to bind and block BMP2, BMP4 and BMP7. At early stages of development, gremlin is expressed in the dorsal and ventral mesoderm in a pattern complementary to that of bmp2, bmp4 and 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 outgrowth. This function appears to be mediated by the neutralization of BMP function to maintain an active AER, to restrict the extension of the areas of programmed cell death and to confine chondrogenesis to the central core mesenchyme of the bud. At the stages of digit formation, gremlin is expressed in the proximal boundary of the interdigital mesoderm of the chick autopod. The anti-apoptotic influence of exogenous Gremlin, which results in the formation of soft tissue syndactyly in the chick, together with the expression of gremlin in the duck interdigital webs, indicates that Gremlin regulates the regression of the interdigital tissue. At later stages of limb development, gremlin is expressed in association with the differentiating skeletal pieces, muscles and the feather buds. The different expression of Gremlin in relation with other BMP antagonists present in the limb bud, such as Noggin, Chordin and Follistatin indicates that the functions of BMPs are regulated specifically by the different BMP antagonists, acting in a complementary fashion rather than being redundant signals.

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Development (Cambridge)

Tập 126 Số 23

5515-5522

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