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We explored the molecular mechanisms of morphological transformations of vertebrate paired fin/limb evolution by comparative gene expression profiling and functional analyses. In this study, we focused on the temporal differences of the onset of  Sonic hedgehog  ( Shh ) expression in paired appendages among different vertebrates. In limb buds of chick and mouse,  Shh  expression is activated as soon as there is a morphological bud, concomitant with  Hoxd10  expression. In dogfish ( Scyliorhinus canicula ), however, we found that  Shh  was transcribed late in fin development, concomitant with  Hoxd13  expression. We utilized zebrafish as a model to determine whether quantitative changes in  hox  expression alter the timing of  shh  expression in pectoral fins of zebrafish embryos. We found that the temporal shift of Shh activity altered the size of endoskeletal elements in paired fins of zebrafish and dogfish. Thus, a threshold level of  hox  expression determines the onset of  shh  expression, and the subsequent heterochronic shift of Shh activity can affect the size of the fin endoskeleton. This process may have facilitated major morphological changes in paired appendages during vertebrate limb evolution.

Heterochronic Shift in Hox-Mediated Activation of Sonic hedgehog Leads to Morphological Changes during Fin Development