Molecular genetic analysis of hindlimb development in zebrafish

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Despite the complexity of human congenital limb formations and their relative abundance, the molecular mechanisms underlying and specific to pelvic fin/hindlimb formation in the zebrafish have largely been unexplored. We propose to unravel the molecular regulation of zebrafish pelvic fin/hindlimb formation using various genetic approaches. To this end, (I) we will clone and examine a novel mutant with severe defects in the formation of pelvic fins and associated endoskeleton, (II) we will test the hypothesis that RA signaling is required for pelvic fin initiation and will examine an unexpected involvement in patterning the pelvic fin endoskeleton, and (III) we will develop transgenic tools that allow us to manipulate RA signaling, and ultimately any signaling pathway, in developing pelvic fins in a tissue-specific manner and at any given time. Together, our work should provide new and significant insights into the regulation of vertebrate hindlimb development. Our findings should be relevant for a better understanding of the underlying mechanisms leading to congenital deformities of tetrapod limbs.