Levels of Gli3 repressor correlate with Bmp4 expression and apoptosis during limb development.
Removal of the posterior wing bud leads to massive apoptosis of the remaining anterior wing bud mesoderm. We show here that this finding correlates with an increase in the level of the repressor form of the Gli3 protein, due to the absence of the Sonic hedgehog (Shh) protein signaling. Therefore, we used the anterior wing bud mesoderm as a model system to analyze the relationship between the repressor form of Gli3 and apoptosis in the developing limb. With increased Gli3R levels, we demonstrate a concomitant increase in Bmp4 expression and signaling in the anterior mesoderm deprived of Shh 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 a correlation between the level of the repressor form of Gli3 and Bmp4 expression in the distal mesoderm. Our analysis adds new insights into the way Shh differentially controls the processing of Gli3 and how, subsequently, BMP4 expression may mediate cell survival or cell death in the developing limb bud in a position-dependent manner.
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, Santander, Spain.
Maria Félix
MF
Bastida
M Dolores
MD
Delgado
Baolin
B
Wang
John F
JF
Fallon
Marian
M
Fernandez-Teran
Maria A
MA
Ros
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D018878:Limb Buds / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000074290:Zinc Finger Protein Gli3; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C065683:GLI3 protein, human; C509239:SHH protein, human