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Publication : Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb.

First Author  Lallemand Y Year  2009
Journal  Dev Biol Volume  331
Issue  2 Pages  189-98
PubMed ID  19422820 Mgi Jnum  J:150759
Mgi Id  MGI:3851667 Doi  10.1016/j.ydbio.2009.04.038
Citation  Lallemand Y, et al. (2009) Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb. Dev Biol 331(2):189-98
abstractText  In tetrapods, the anteroposterior (AP) patterning of the limb is under the control of the antagonistic activities of the secreted factor Sonic hedgehog (Shh) and Gli3R, the truncated repressor form of the transcription factor Gli3. In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R. Consequently, in Shh null mutants, Msx genes are overexpressed and, furthermore, partially responsible for the limb phenotype. This is exemplified by the fact that reducing Msx activity in Shh mutants partially restores a normal limb development. Finally, we show that the main action of the Msx genes, in both normal and Shh(-/-) limb development, is to control cell death in the mesenchyme. We propose that, in the limb, Msx genes act downstream of the Shh/Gli3 pathway by transducing BMP signaling and that, in the absence of Shh signaling, their deregulation contributes to the extensive apoptosis that impairs limb development.
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