Approaches to a Comparison of Fin and Limb Structure and Development

Abstract

Carl Gegenbaur (1865) proposed a specific arrangement of endoskeletal elements as the key feature of a common plan of vertebrate paired appendages which he called the metapterygium. He based the recognition of a metapterygium in different species on endoskeletal pattern but not on its position within the fin/limb. Here I suggest to use the position of Gegenbaur’s metapterygium defined by position of its precursor cells in the fin bud to evaluate homology of metapterygia. The results of developmental studies do not yet bridge the gap between patterning mechanisms and endoskeletal patterns in fins and limbs. Of all genes involved in fin and limb development, the function of Hoxa and Hoxa genes is most closely linked to endoskeleton formation. However, their downstream targets are unknown and it is thus not clear how differences in their expression patterns relate to different skeletal patterns in different species. A comparison of gene function has become possible, however, by the analysis of zebrafish and mouse mutants affecting orthologous genes. Shh and the transcription factor dHand are required for anterior-posterior patterning of fins and limbs. Comparative analysis shows that the initial polarization of the buds involves the action of dHand in both species. Subsequently Shh acts on maintenance and initiation of gene expression along the anterior-posterior axis. Shh maintains developmental progress by interacting with Fgf signalling molecules originating from the ectoderm. However, in spite of general similarities differences exist at the level of Fgf regulation by Shh. In the zebrafish, Shh acts to induce Fgf4 and Fgf8 expression while in the mouse Shh maintains expression of three Fgf genes and Fgf8 expression has escaped Shh regulation. Because Fgfs are important regulators of cell type identity, this difference in Fgf regulation may account for the different proximal-distal extent to which fin and limb buds develop in Shh mutant larvae and pups, respectively.