|Presenting Author(s)||Marian Ros|
|Abstract Title||The GLI3 repressor form acts through BMP4 in the induction of apoptosis during limb development.|
|Full author List||Maria Félix Bastida, M. Dolores Delgado, Baolin Wang, John F. Fallon, Marian Fernandez-Teran and Maria A. Ros|
|Text of abstract||
During vertebrate limb development Shh signaling prevents the processing of the full length Gli3 to a short form that functions as a strong repressor. This repressor form of Gli3 (Gli3R) is present in an anterior-posterior gradient with the highest levels in the anterior part of the limb bud where Shh signaling is at minimum. The genetic data of the Shh, Gli3 and double compound mutants indicate that the phenotype in the absence of Shh is caused by an excess in the Gli3R form that interferes with normal gene expression and cell survival.Here we have investigated the correlation between the level of Gli3R and cell death using the anterior half of the chick wing bud, experimentally deprived of Shh signaling, as model system. Deprived of Shh signaling, the anterior mesoderm suffers massive apoptosis that precludes further realization of its normal fate. In parallel with the increase in apoptosis, we detect a two-fold increase in the level of the Gli3R form as well as upregulation in Bmp4 expression and signaling. Several experimental approaches show that the apoptosis can be prevented by exogenous Noggin indicating that Bmp signaling mediates it. The analysis of Bmp4 expression in several mouse and chick mutations with defects in either expression or processing of Gli3 indicates that it is downstream of Gli3R in the anterior-distal mesoderm. Our results are discussed in the context of Shh's control of cell survival and cell death in the developing limb bud.
|Which session is your work most relevant to:||Limb evolution|
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