A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways

Developmental Biology
Vanessa Zuzarte-LuisJ M Hurle

Abstract

In an attempt to identify new genes implicated in the control of programmed cell death during limb development, we have generated a cDNA library from the regressing interdigital tissue of chicken embryos. We have analyzed 804 sequences from this library and identified 23 genes involved in apoptosis in different models. One of the genes that came up in the screening was the Bone Morphogenetic Protein family member, Bmp5, that has not been previously involved in the control of apoptosis during limb development. In agreement with a possible role in the control of cell death, Bmp5 exhibited a regulated pattern of expression in the interdigital tissue. Transcripts of Bmp5 and BMP5 protein were abundant within the cytoplasm of the fragmenting apoptotic interdigital cells in a way suggesting that delivery of BMPs into the tissue is potentiated during apoptosis. Gain-of-function experiments demonstrated that BMP5 has the same effect as other interdigital BMPs inducing apoptosis in the undifferentiated mesoderm and growth in the prechondrogenic mesenchyme. We have characterized both Smad proteins and MAPK p38 as intracellular effectors for the action of BMPs in the developing limb autopod. Activation of Smad signaling involves the recep...Continue Reading

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