Shh/Gremlin/Fgf regulatory network genes are expressed during both fin and urogenital development in paddlefish

In humans, congenital birth defects in limbs (e.g. arms & legs, hand & feet, and the digits) are often observed in syndromic association with abnormalities in the urogenital system (internal and external reproductive anatomy, the urinary tract, and kidneys). Experimental studies in the mouse, as a proxy for human development, reveal that genes in the Shh/Gremlin/Fgf gene regulatory network interact to promote proper outgrowth and differentiation of tissues in both of these organ systems. Recent data from our lab has revealed that genes in this network are similarly expressed in the paired fins (homologs of limbs) of the “living fossil” American paddlefish Polyodon spathula, a useful outgroup comparator to the derived model system vertebrates. However, what remains unexplored is whether these same genes also play a role in the development of the urogenital system in paddlefish. To address this question, we used a combination of RNA in situ hybridization and cryosection histology to determine the expression patterns of many network genes during development of the tissues of interest. We assayed developing paddlefish embryos for the genes Sonic Hedgehog (Shh); the Shh receptors Ptch1 and Ptch2, the Shh response elements Gli1 and Gli3, and the Shh regulators Bmp4 and Fgf4. Our results demonstrate similar gene sharing in paddlefish and mammals, supporting the hypothesis that the Shh/Gremlin/Fgf network is a conserved organ patterning mechanism common to all jawed vertebrates