title: Transgenic analysis of Hoxd gene regulation during digit development.
abstract: In tetrapods, posterior Hoxd genes (from groups 10 to 13) are necessary to properly pattern the developing autopods, including the number and identities of digits. Their coordinated expression is achieved by sharing a global control region (GCR), which was isolated and localized 200 kb 5' (centromeric) of the gene cluster. However, in transgenic assays, the GCR was unable to fully recapitulate all aspects of the endogenous Hoxd expression patterns during distal limb development. In this paper, we further analyze the regulatory potential of this locus and report the characterization of Prox, a second enhancer element that contributes to the transcriptional activity of posterior Hoxd genes in developing distal limb buds. We show that the GCR and Prox elements complement each other and work in combination to correctly establish the late phase of Hoxd genes expression. Based on DNA sequence conservation and transgenic assays, we discuss the functions of these regulatory regions as well as a potential evolutionary scheme accounting for their emergence along with the evolution of tetrapod limbs.
authors: National Center for Competence in Research/Frontiers in Genetics, Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors: Federico
authors: F
authors: Gonzalez
authors: Denis
authors: D
authors: Duboule
authors: François
authors: F
authors: Spitz
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000196:embryology; D022202:Chromosomes, Artificial, Bacterial; D019143:Evolution, Molecular; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D010957:Plasmids / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D019076:Transgenes
chemical_list: D018398:Homeodomain Proteins; C486697:Hoxd1 protein, mouse