10 Premature regression of the leg apical ectodermal ridge (AER) in the Japanese chick wingless mutant

The autosomal dominant Japanese wingless mutant has varying degrees of wing and leg truncations. The wing phenotype is more severe, usually being characterised by complete loss of the radius, ulna and digits. In contrast the leg abnormalities are usually characterised by the loss of only the most distal structures: the toe nails and one or two of the distal phalanges. Previous investigations have shown that in the developing wing the AER, which controls outgrowth, is not maintained. To understand the leg defect, we have characterised its development at both a molecular and cellular level. Our first analysis showed the severity of wing defect correlated with the leg defects. Scanning and transmission electron microscopy together with molecular analyses showed that the leg AER degenerates at stage 28 and this is later associated with the early onset of cell death in the underlying mesenchyme between stages 31–32. This is slightly earlier than in the wildtype leg where AER regression and cell death occurs almost simultaneously at stages 33–34. Thus premature loss of the AER function is likely to result in the loss of the toe nails/phalanges. To confirm this we removed the AER in wildtype embryos and followed the fate of the limb. This also resulted in premature cell death and limb truncations equivalent to that observed in mutant limbs. Thus, as in the wing, the abnormalities are a consequence of defective AER maintenance and/or function, although the onset occurs much later during development.