Hoxd13/Bmp2-mediated mechanism involved in zebrafish finfold design

Abstract

AbstractThe overexpression ofhoxd13aduring zebrafish fin development causes distal endochondral expansion and simultaneous reduction of the finfold, mimicking the major events thought to have happened during the fin-to-limb transition in Vertebrates. We investigated the effect ofhoxd13aoverexpression on putative downstream targets and found it to cause downregulation of proximal fin identity markers (meis1andemx2) and upregulation of genes involved in skeletogenesis/patterning (fbn1,dacha) and AER/Finfold maintenance (bmps). We then show thatbmp2boverexpression leads to finfold reduction, recapitulating the phenotype observed inhoxd13a-overexpressing fins. In addition, we show that during the development of the long finfold in leot1/lofdt1mutants,hoxd13aandbmp2bare downregulated. Our results suggest that modulation of the transcription factor Hoxd13 during evolution may have been involved in finfold reduction through regulation of the Bmp signalling that then activated apoptotic mechanisms impairing finfold elongation.