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Denis Duboule

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Related publications (58)

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Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development

Denis Duboule, Marion Leleu

Background: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation ...

2018

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Denis Duboule

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with larg ...

2017

Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes

Denis Duboule, Lucille Delisle

Background The spatial organization of the mammalian genome relies upon the formation of chromatin domains of various scales. At the level of gene regulation in cis, collections of enhancer sequences define large regulatory landscapes that usually match wi ...

2019

Atypical relaxation of structural constraints in Hox gene clusters of the green anole lizard

Denis Duboule

Hox genes control many aspects of embryonic development in metazoans. Previous analyses of this gene family revealed a surprising diversity in terms of gene number and organization between various animal species. In vertebrates, Hox genes are grouped into ...

2009

Induction of a chromatin boundary in vivo upon insertion of a tad border

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

Author summary During development, enhancer sequences tightly regulate the spatio-temporal expression of target genes often located hundreds of kilobases away. This complex process is made possible by the folding of chromatin into domains, which are separa ...

2021

Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of HOXD1 for Horn Patterning in Bovidae

Denis Duboule

In the course of evolution, pecorans (i.e., higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as "headgear," which likely share the same origin and genetic basis. However, the nature and function of ...

OXFORD UNIV PRESS2021

Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape

Denis Duboule, Guillaume Andrey, Anamaria Necsulea

Vertebrate Hox genes encode transcription factors operating during the development of multiple organs and structures. However, the evolutionary mechanism underlying this remarkable pleiotropy remains to be fully understood. Here, we show that Hoxd8 and Hox ...

National Academy of Sciences2016

Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos

Denis Duboule, Lucille Delisle, Alexandre Gauthier Aurèle Mayran, Dominique Anne Sarah Kolly

Understanding the interplay between cell fate specification and morphogenetic changes remains a challenge in developmental biology. Gastruloids, stem cell models of postimplantation mammalian development, provide a platform to address this question. Here, ...

American Association for the Advancement of Science (AAAS)2025

CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length

Denis Duboule, Fabrice Daniel Darbellay, Lucille Delisle, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Célia Corinne Renée Bochaton, Pierre Osteil

Mammalian tail length is controlled by several genetic determinants, among which are Hox13 genes, whose function is to terminate the body axis. Accordingly, the precise timing in the transcriptional activation of these genes may impact upon body length. Un ...

National Academy of Sciences2024

Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine

Denis Duboule

Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thor ...

National Academy of Sciences2013

Characterization of mouse Dactylaplasia mutations: a model for human ectrodactyly SHFM3

Denis Duboule, Marc Samuel Friedli

SHFM3 is a limb malformation characterized by the absence of central digits. It has been shown that this condition is associated with tandem duplications of about 500 kb at 10q24. The Dactylaplasia mice display equivalent limb defects and the two correspon ...

2008

Sequential in cis mutagenesis in vivo reveals various functions for CTCF sites at the mouse HoxD cluster

Denis Duboule, Lucille Delisle

In this study, Amandio et al. sought to understand the functions of the highly conserved CTCF sites distributed over the Hox gene clusters. The authors produced an allelic series of cumulative in cis mutations in these sites, up to the abrogation of CTCF b ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2021

A switch between topological domains underlies HoxD genes collinearity in mouse limbs

Didier Trono, Denis Duboule, Marion Leleu, Guillaume Andrey

Hox genes are major determinants of the animal body plan, where they organize structures along both the trunk and appendicular axes. During mouse limb development, Hoxd genes are transcribed in two waves: early on, when the arm and forearm are specified, a ...

American Association for the Advancement of Science2013

Epigenetic temporal control of mouse Hox genes in vivo

Denis Duboule

During vertebrate development, the temporal control of Hox gene transcriptional activation follows the genomic order of the genes within the Hox clusters. Although it is recognized that this "Hox clock" serves to coordinate body patterning, the underlying ...

American Association for the Advancement of Science2009

Bimodal control of Hoxd gene transcription in the spinal cord defines two regulatory subclusters

Denis Duboule

The importance of Hox genes in the specification of neuronal fates in the spinal cord has long been recognized. However, the transcriptional controls underlying their collinear expression domains remain largely unknown. Here we show in mice that the corres ...

2012

Epigenetic regulation of Hox gene activation: the waltz of methyls

Denis Duboule

Genetic studies have revealed that the antagonistic interplay between PcG and TrxG/MLL complexes is essential for the proper maintenance of vertebrate Hox gene expression in time and space. Hox genes must be silenced in totipotent embryonic stem cells and, ...

2008

Visualizing the HoxD Gene Cluster at the Nanoscale Level

Denis Duboule, Suliana Manley, Aleksandr Benke

Transcription of HoxD cluster genes in limbs is coordinated by two topologically associating domains (TADs), neighboring the cluster and containing various enhancers. Here, we use a combination of microscopy approaches and chromosome conformation capture t ...

2015

The role of Hox genes during vertebrate limb development

Denis Duboule

The potential role of Hox genes during vertebrate limb development was brought into focus by gene expression analyses in mice (P Dolle, JC Izpisua-Belmonte, H Falkenstein, A Renucci, D Duboule, Nature 1989, 342:767-772), at a time when limb growth and patt ...

2007

The rise and fall of Hox gene clusters

Denis Duboule

Although all bilaterian animals have a related set of Hox genes, the genomic organization of this gene complement comes in different flavors. In some unrelated species, Hox genes are clustered; in others, they are not. This indicates that the bilaterian an ...

2007

Mesomelic dysplasias associated with the HOXD locus are caused by regulatory reallocations

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

Mesomelic dysplasia, a severe shortening and bending of the limb, has been linked to rearrangements in the HoxD cluster in humans and mice. Here the authors engineer a 1 Mb inversion including the HoxD gene cluster and use this model to provide a mechanist ...

Nature Portfolio2021