title: TGF-beta is required for programmed cell death in interdigital webs of the developing mouse limb.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, Building 61, University of Saarland, D-66421, Homburg/Saar, Germany. nduenke@gwdg.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Dünker
authors.forename: Kai
authors.initials: K
authors.lastname: Schmitt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
mesh_terms: 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
chemical_list: 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