Browsing by Author "Duboule, Denis"
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- Reorganisation ofHoxdregulatory landscapes during the evolution of a snake-like body planPublication . Guerreiro, Isabel; Gitto, Sandra; Novoa, Ana; Codourey, Julien; Nguyen Huynh, Thi Hanh; Gonzalez, Federico; Milinkovitch, Michel C; Mallo, Moises; Duboule, DenisWithin land vertebrate species, snakes display extreme variations in their body plan, characterized by the absence of limbs and an elongated morphology. Such a particular interpretation of the basic vertebrate body architecture has often been associated with changes in the function or regulation of Hox genes. Here, we use an interspecies comparative approach to investigate different regulatory aspects at the snake HoxD locus. We report that, unlike in other vertebrates, snake mesoderm-specific enhancers are mostly located within the HoxD cluster itself rather than outside. In addition, despite both the absence of limbs and an altered Hoxd gene regulation in external genitalia, the limb-associated bimodal HoxD chromatin structure is maintained at the snake locus. Finally, we show that snake and mouse orthologous enhancer sequences can display distinct expression specificities. These results show that vertebrate morphological evolution likely involved extensive reorganisation at Hox loci, yet within a generally conserved regulatory framework.
- Tail Bud Progenitor Activity Relies on a Network Comprising Gdf11, Lin28, and Hox13 GenesPublication . Aires, Rita; de Lemos, Luisa; Nóvoa, Ana; Jurberg, Arnon Dias; Mascrez, Bénédicte; Duboule, Denis; Mallo, MoisésDuring the trunk-to-tail transition, axial progenitors relocate from the epiblast to the tail bud. Here, we show that this process entails a major regulatory switch, bringing tail bud progenitors under Gdf11 signaling control. Gdf11 mutant embryos have an increased number of such progenitors that favor neural differentiation routes, resulting in a dramatic expansion of the neural tube. Moreover, inhibition of Gdf11 signaling recovers the proliferation ability of these progenitors when cultured in vitro. Tail bud progenitor growth is independent of Oct4, relying instead on Lin28 activity. Gdf11 signaling eventually activates Hox genes of paralog group 13, which halt expansion of these progenitors, at least in part, by down-regulating Lin28 genes. Our results uncover a genetic network involving Gdf11, Lin28, and Hox13 genes controlling axial progenitor activity in the tail bud.