Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates

• DOI: 10.1016/j.cub.2021.09.010
• Publication Date: 2021-10-04T23:10:31Z
• Authors: Anna Trofka; Bau-Lin Huang; Jianjian Zhu; William F. Heinz; Valentin Magidson; Yuki Shibata; Yun-Bo Shi; Basile Tarchini; H. Scott Stadler; Mirindi Kabangu; Nour W. Al Haj Ba...; S. Randal Voss; Susan Mackem
• Keywords: Limb development; Apical ectodermal ridge

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius tibia), followed by digit-appearance order continuing polarity. The only exceptions are urodele amphibians (salamanders), whose develop preaxial polarity who also notable for unique ability regenerate complete limbs adults. mechanistic basis this dominance has remained an enigma even been proposed relate the acquisition of novel genes involved in regeneration. However, recent fossil evidence suggests that represents ancestral rather than derived state. Here, we report 5′Hoxd (Hoxd11-d13) gene deletion mouse is atavistic uncovers underlying mammalian formation. We demonstrate shift from results excess Gli3 repressor (Gli3R) activity due loss 5′Hoxd-Gli3 antagonism associated cell-cycle changes promoting precocious exit bud. further show knockdown axolotl a dominant skeleton formation, well expanded paddle-shaped limb-bud morphology ensuing polydactyly. Evolutionary Gli3R level, which played key role fin-to-limb transition, be fundamental formation skeleton.