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First published online May 30, 2007

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The web of death

Programmed cell death (PCD) in the interdigit region of developing vertebrate limbs generates separated rather than webbed digits. Previous models have proposed that bone morphogenetic proteins (BMPs) directly trigger such PCD; however, they might also act indirectly by regulating fibroblast growth factors (FGFs), which act as cell survival factors. To investigate this question, Mark Lewandoski's group inactivated the BMP receptor gene Bmpr1a specifically in the limb bud's apical ectodermal ridge (AER) - a source of FGF activity. They report on p. 2359 that in mice, BMP signalling mediates AER induction. However, it subsequently inhibits the expression of the AER survival factors Fgf4 and Fgf8, leading to interdigit PCD. By generating conditional mutant mice, the authors show that Bmpr1a inactivation induces Fgf4 and Fgf8 upregulation in the AER. Webbing persists in mice where Bmpr1a and Fgf8 are inactivated, but disappears when one copy of Fgf4 is also inactivated. Evolutionary alterations in AER FGF activity might account for changes in limb morphology in different species.

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Related articles in Development:

BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling

Sangeeta Pajni-Underwood, Catherine P. Wilson, Cindy Elder, Yuji Mishina, and Mark Lewandoski
Development 2007 134: 2359-2368. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?