TGF-beta is required for programmed cell death in interdigital webs of the developing mouse limb.
During limb formation massive cell death in the mesenchyme of the interdigital spaces accompanies the formation of free digits. Members of the transforming growth factor beta (TGF-) superfamily were discussed to play a key role in cell-cell interactions, important in the regulation of programmed cell death (PCD). TGF-beta itself is believed to be involved in epithelial-mesenchymal interactions. Here, we demonstrate that PCD is significantly reduced in interdigital spaces of the developing limbs of Tgfbeta2-/-Tgfbeta3-/- double knockouts. The regression of interdigital webs seems to be doses-dependent as interdigital mesenchyme is at least partly reduced in Tgfbeta2-/-Tgfbeta3+/- mutants, whereas interdigital zones of Tgfbeta2-/-Tgfbeta3-/- double knockouts reveal only minimal signs of regression. We conclude that TGF- is a critical extrinsic regulator of PCD.
Dünker
Nicole
N
Department of Anatomy and Cell Biology, Building 61, University of Saarland, D-66421, Homburg/Saar, Germany. nduenke@gwdg.de
Schmitt
Kai
K
Krieglstein
Kerstin
K
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D019902:Chondrocytes / Q000378:metabolism; D004789:Enzyme Activation; D005121:Extremities / Q000196:embryology*; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases