Mostrando recursos 1 - 12 de 12

  1. Oct4 Is a Key Regulator of Vertebrate Trunk Length Diversity

    Aires, Rita; Jurberg, Arnon D.; Leal, Francisca; Nóvoa, Ana; Cohn, Martin J.; Mallo, Moisés
    The deposited article version is a post-print version (final draft post-refereeing) and included supplementary information.

  2. Reorganisation ofHoxdregulatory landscapes during the evolution of a snake-like body plan

    Guerreiro, Isabel; Gitto, Sandra; Novoa, Ana; Codourey, Julien; Nguyen Huynh, Thi Hanh; Gonzalez, Federico; Milinkovitch, Michel C; Mallo, Moises; Duboule, Denis
    Within 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...

  3. Revisiting the involvement of signaling gradients in somitogenesis

    Mallo, Moisés
    During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites. Somites are sequentially formed at the anterior end of the presomitic mesoderm (PSM) resulting from functional interactions between the oscillatory activity of signals promoting segmentation and a moving wavefront of tissue competence to those signals, eventually generating a constant flow of new somites at regular intervals. According to the current model for somitogenesis, the wavefront results from the combined activity of two opposing functional gradients in the PSM involving the Fgf, Wnt and retinoic acid (RA) signaling pathways. Here,...

  4. Compartment-dependent activities of Wnt3a/β-catenin signaling during vertebrate axial extension

    Jurberg, Arnon Dias; Aires, Rita; Nóvoa, Ana; Rowland, Jennifer Elizabeth; Mallo, Moisés
    Extension of the vertebrate body results from the concerted activity of many signals in the posterior embryonic end. Among them, Wnt3a has been shown to play relevant roles in the regulation of axial progenitor activity, mesoderm formation and somitogenesis. However, its impact on axial growth remains to be fully understood. Using a transgenic approach in the mouse, we found that the effect of Wnt3a signaling varies depending on the target tissue. High levels of Wnt3a in the epiblast prevented formation of neural tissues, but did not impair axial progenitors from producing different mesodermal lineages. These mesodermal tissues maintained a remarkable...

  5. Controlling Hox gene expression and activity to build the vertebrate axial skeleton

    Casaca, Ana; Santos, Ana Cristina; Mallo, Moisés
    It has long been known that Hox genes are central players in patterning the vertebrate axial skeleton. Extensive genetic studies in the mouse have revealed that the combinatorial activity of Hox genes along the anterior-posterior body axis specifies different vertebral identities. In addition, Hox genes were instrumental for the evolutionary diversification of the vertebrate body plan. In this review, we focus on fundamental questions regarding the intricate mechanisms controlling Hox gene activity. In particular, we discuss the functional relevance of the precise timing of Hox gene activation in the embryo. Moreover, we provide insight into the epigenetic regulatory mechanisms that...

  6. The regulation of Hox gene expression during animal development

    Mallo, M.; Alonso, C. R.
    Hox genes encode a family of transcriptional regulators that elicit distinct developmental programmes along the head-to-tail axis of animals. The specific regional functions of individual Hox genes largely reflect their restricted expression patterns, the disruption of which can lead to developmental defects and disease. Here, we examine the spectrum of molecular mechanisms controlling Hox gene expression in model vertebrates and invertebrates and find that a diverse range of mechanisms, including nuclear dynamics, RNA processing, microRNA and translational regulation, all concur to control Hox gene outputs. We propose that this complex multi-tiered regulation might contribute to the robustness of Hox expression...

  7. Switching Axial Progenitors from Producing Trunk to Tail Tissues in Vertebrate Embryos

    Jurberg, Arnon Dias; Aires, Rita; Varela-Lasheras, Irma; Nóvoa, Ana; Mallo, Moisés
    The vertebrate body is made by progressive addition of new tissue from progenitors at the posterior embryonic end. Axial extension involves different mechanisms that produce internal organs in the trunk but not in the tail. We show that Gdf11 signaling is a major coordinator of the trunk-to-tail transition. Without Gdf11 signaling, the switch from trunk to tail is significantly delayed, and its premature activation brings the hindlimbs and cloaca next to the forelimbs, leaving extremely short trunks. Gdf11 activity includes activation of Isl1 to promote formation of the hindlimbs and cloaca-associated mesoderm as the most posterior derivatives of lateral mesoderm...

  8. Transient Activation of Meox1 Is an Early Component of the Gene Regulatory Network Downstream of Hoxa2

    Kirilenko, P.; He, G.; Mankoo, B. S.; Mallo, M.; Jones, R.; Bobola, N.
    Hox genes encode transcription factors that regulate morphogenesis in all animals with bilateral symmetry. Although Hox genes have been extensively studied, their molecular function is not clear in vertebrates, and only a limited number of genes regulated by Hox transcription factors have been identified. Hoxa2 is required for correct development of the second branchial arch, its major domain of expression. We now show that Meox1 is genetically downstream from Hoxa2 and is a direct target. Meox1 expression is downregulated in the second arch of Hoxa2 mouse mutant embryos. In chromatin immunoprecipitation (ChIP), Hoxa2 binds to the Meox1 proximal promoter. Two...

  9. Evidence for a Myotomal Hox/Myf Cascade Governing Nonautonomous Control of Rib Specification within Global Vertebral Domains

    Vinagre, Tânia; Moncaut, Natalia; Carapuço, Marta; Nóvoa, Ana; Bom, Joana; Mallo, Moisés
    Hox genes are essential for the patterning of the axial skeleton. Hox group 10 has been shown to specify the lumbar domain by setting a rib-inhibiting program in the presomitic mesoderm (PSM). We have now produced mice with ribs in every vertebra by ectopically expressing Hox group 6 in the PSM, indicating that Hox genes are also able to specify the thoracic domain. We show that the information provided by Hox genes to specify rib-containing and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression. This information is then transmitted to the...

  10. Hox genes and regional patterning of the vertebrate body plan

    Mallo, Moises; Wellik, Deneen M.; Deschamps, Jacqueline
    Several decades have passed since the discovery of Hox genes in the fruit fly Drosophila melanogaster. Their unique ability to regulate morphologies along the anteroposterior (AP) axis (Lewis, 1978) earned them well-deserved attention as important regulators of embryonic development. Phenotypes due to loss- and gain-of-function mutations in mouse Hox genes have revealed that the spatio-temporally controlled expression of these genes is critical for the correct morphogenesis of embryonic axial structures. Here, we review recent novel insight into the modalities of Hox protein function in imparting specific identity to anatomical regions of the vertebral column, and in controlling the emergence of...

  11. Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity

    Casaca, Ana; Nóvoa, Ana; Mallo, Moisés
    Formation of the vertebrate axial skeleton requires coordinated Hox gene activity. Hox group 6 genes are involved in the formation of the thoracic area owing to their unique rib-promoting properties. Here we show that the linker region (LR) connecting the homeodomain and the hexapeptide is essential for Hoxb6 rib-promoting activity in mice. The LR-defective Hoxb6 protein was still able to bind a target enhancer together with Pax3, producing a dominant-negative effect, indicating that the LR brings additional regulatory factors to target DNA elements. We also found an unexpected association between Hoxb6 and segmentation in the paraxial mesoderm. In particular, Hoxb6...

  12. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone

    van de Ven, C.; Bialecka, M.; Neijts, R.; Young, T.; Rowland, J. E.; Stringer, E. J.; Van Rooijen, C.; Meijlink, F.; Novoa, A.; Freund, J.-N.; Mallo, M.; Beck, F.; Deschamps, J.
    Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects, including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele...

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