%0 Journal Article %T A relative shift in cloacal location repositions external genitalia in amniote evolution %+ Harvard Medical School [Boston] (HMS) %+ Harvard University %+ Dana-Farber Cancer Institute [Boston] %+ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) %+ Brigham and Women's Hospital [Boston] %+ Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology %A Tschopp, Patrick %A Sherratt, Emma %A Sanger, Thomas, J %A Groner, Anna, C. %A Aspiras, Ariel, C %A Hu, Jimmy, K %A Pourquié, Olivier, P %A Gros, Jerome %A Tabin, Clifford, J %Z P.T. was supported by post-doctoral fellowships from the Swiss National Science Foundation, EMBO and the Human Frontiers Science Program. A.C.G. was supported by a post-doctoral fellowship from the Swiss National Science Foundation. This work was supported by NIH grant R37-HD032443 to C.J.T. %Z The publisher's final edited version of this article is available at Nature. %< avec comité de lecture %@ 0028-0836 %J Nature %I Nature Publishing Group %V 516 %N 7531 %P 391-394 %8 2014-12-18 %D 2014 %R 10.1038/nature13819 %M 25383527 %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/Development Biology %Z Life Sciences [q-bio]/Development Biology/Embryology and OrganogenesisJournal articles %X The move of vertebrates to a terrestrial lifestyle required major adaptations in their locomotory apparatus and reproductive organs. While the fin-to-limb transition has received considerable attention, little is known about the developmental and evolutionary origins of external genitalia. Similarities in gene expression have been interpreted as a potential evolutionary link between the limb and genitals; however, no underlying developmental mechanism has been identified. We re-examined this question using micro-computed tomography, lineage tracing in three amniote clades, and RNA-sequencing-based transcriptional profiling. Here we show that the developmental origin of external genitalia has shifted through evolution, and in some taxa limbs and genitals share a common primordium. In squamates, the genitalia develop directly from the budding hindlimbs, or the remnants thereof, whereas in mice the genital tubercle originates from the ventral and tail bud mesenchyme. The recruitment of different cell populations for genital outgrowth follows a change in the relative position of the cloaca, the genitalia organizing centre. Ectopic grafting of the cloaca demonstrates the conserved ability of different mesenchymal cells to respond to these genitalia-inducing signals. Our results support a limb-like developmental origin of external genitalia as the ancestral condition. Moreover, they suggest that a change in the relative position of the cloacal signalling centre during evolution has led to an altered developmental route for external genitalia in mammals, while preserving parts of the ancestral limb molecular circuitry owing to a common evolutionary origin. %G English %Z The authors thank D. Duboule, H. Kaessmann, A. Necsulea, B. Okaty, G. Rey and G. P. Wagner for discussions, M. A. de Bakker for the snake Tbx5 probe and A. M. Herrera and M. J. Cohn for discussing and sharing unpublished results. μCT scans were performed at the Center for Nanoscale Systems, Harvard University (supported by National Science Foundation award ECS-0335765) and at the Museum of Comparative Zoology. Next-generation sequencing was performed at the HMS Biopolymers Facility and computational analyses were run on the Orchestra Cluster, HMS Research Computing. %2 https://pasteur.hal.science/pasteur-01976104/document %2 https://pasteur.hal.science/pasteur-01976104/file/Tschopp_Nature.pdf %L pasteur-01976104 %U https://pasteur.hal.science/pasteur-01976104 %~ PASTEUR %~ CNRS %~ IGBMC %~ UNIV-STRASBG %~ SITE-ALSACE