Making the connection: exploring classical concepts in normal and abnormal limb development using contemporary approaches.

Classical studies of the vertebrate limb have provided a firm foundation for recent investigations into the molecular control of mechanisms governing limb patterning. The early studies revealed the importance of inductive tissue interactions in developing systems, the spatiotemporal restrictions of these interactions, and the conservation of inductive signals between different tissues and even different species. They incorporated a number of different experimental approaches, including: homologous and heterologous tissue grafting and recombination, the investigation of several limb mutations, and examination of the response of normal limb tissue to a variety of teratogenic treatments. While some of the mutations studied only affected the limbs, most were highly pleiotropic, producing complex syndromes that altered the development of several embryonic structures in addition to the limbs. Some of these syndromes could be partially or completely phenocopied (mimicked) by specific chemical or physical treatments. One such gene-phenocopy pairing that we have studied is that of the mutation wingless-2 and the syndrome produced by treatment with retinoic acid. Another aspect of abnormal pattern formation we explored is the interaction between wingless-2 and eudiplopodia.