The role of morphogenetic cell death during abnormal limb-bud outgrowth in XXXX heterozygous for the dominant mutation @entity4219 ( @entity4219 ).

@entity19 @entity4218 @entity4219 @entity13258 @entity528
A dominant mutation in the @entity19 , @entity4219 ( @entity4219 ), induces @entity4218 in heterozygotes. Typical expression includes axial shortening of the radius, tibia and talus (' @entity4219 '), with supernumerary metacarpals, metatarsals, and digits ('polydactyly'). Pathogenesis was investigated during developmental stages 16 through 22 (11th through 15th days of gestation). Full expression was apparent during stage 20 when the limb pattern was comprised of pre-cartilaginous anlagen. Formation of a pre-axial protrusion on the autopod during stage 17 or 18 was the earliest gross abnormality, and foreshadowed the development of @entity13258 . Microscopically, there was an alteration in the pattern of @entity528 ( @entity528 ) programmed to occur within the zeugopod and autopod. The 'opaque patch' (mesodermal necrotic zone normally occurring between tibial and fibular anlagen) was overextended pre-axially causing resorption of the tibial precartilage. Additionally, @entity528 normally occurring within the basal cell layer of the apical ectodermal ridge (AER) and the 'foyer primaire pr  axial' was not expressed in the mutant autopod. This occurred in association with outgrowth of the protrusion. The pre-axial portion of the AER remained in an abnormally thickened, viable, proliferative state, and did not undergo scheduled degression. This may have been the basis for prolonged induction of pre-axial outgrowth. Paucity of mesenchymal cell filopodial processes extended along the basal lamina, as well as a rarefaction of the filamentous material normally associated with the mesodermal face of the basal lamina, was detected at the pre-axial AER-mesenchymal interface on stage 18. A potential involvement of epithelial-mesenchymal interactions in the induction of epithelial @entity528 is discussed.
