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

Autor:	Trofka A; Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA., Huang BL; Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA., Zhu J; Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA., Heinz WF; Optical Microscopy and Analysis Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Magidson V; Optical Microscopy and Analysis Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Shibata Y; Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver NICHD, Bethesda, MD, USA., Shi YB; Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver NICHD, Bethesda, MD, USA., Tarchini B; The Jackson Laboratory, Bar Harbor, ME, USA., Stadler HS; Division of Skeletal Biology, Shriners Hospitals for Children, Portland, OR, USA; Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, OR, USA., Kabangu M; Department of Neuroscience, Spinal Cord and Brain Injury Research Center, and Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY, USA., Al Haj Baddar NW; Department of Neuroscience, Spinal Cord and Brain Injury Research Center, and Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY, USA., Voss SR; Department of Neuroscience, Spinal Cord and Brain Injury Research Center, and Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY, USA. Electronic address: srvoss@uky.edu., Mackem S; Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA. Electronic address: mackems@mail.nih.gov.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2021 Nov 22; Vol. 31 (22), pp. 4923-4934.e5. Date of Electronic Publication: 2021 Oct 04.
DOI:	10.1016/j.cub.2021.09.010
Abstrakt:	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 and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults. The mechanistic basis for this preaxial dominance has remained an enigma and has even been proposed to relate to the acquisition of novel genes involved in regeneration. However, recent fossil evidence suggests that preaxial polarity represents an ancestral rather than derived state. Here, we report that 5'Hoxd (Hoxd11-d13) gene deletion in mouse is atavistic and uncovers an underlying preaxial polarity in mammalian limb formation. We demonstrate this shift from postaxial to preaxial dominance in mouse results from excess Gli3 repressor (Gli3R) activity due to the loss of 5'Hoxd-Gli3 antagonism and is associated with cell-cycle changes promoting precocious cell-cycle exit in the anterior limb bud. We further show that Gli3 knockdown in axolotl results in a shift to postaxial dominant limb skeleton formation, as well as expanded paddle-shaped limb-bud morphology and ensuing polydactyly. Evolutionary changes in Gli3R activity level, which also played a key role in the fin-to-limb transition, appear to be fundamental to the shift from preaxial to postaxial polarity in formation of the tetrapod limb skeleton. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu