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Denis Duboule

Cette personne a quitté l’EPFL

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Publications associées (58)

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Tinkering with constraints in the evolution of the vertebrate limb anterior-posterior polarity

Denis Duboule

Genes belonging to both HoxA and HoxD clusters are required for proper vertebrate limb development. Mice lacking all, or parts of, Hoxa and Hoxd functions in forelimbs, as well as mice with a gain of function of these genes in the early limb bud, have help ...

2007

A complex regulatory landscape involved in the development of mammalian external genitals

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer-enhancer and enhancer-promoter interactions. ...

2020

The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes

Denis Duboule, Lucille Delisle

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas ...

2017

Long-range enhancer-promoter interactions in the HoxD complex

Denis Duboule

Collinear expression of 5′ Hoxd genes during mammalian limb development is required to properly determine digits number and identity. We recently proposed a two-step model to account for the underlying regulatory mechanism, which involves an initial loopin ...

Elsevier Science BV2009

Large scale genomic reorganization of topological domains at the HoxD locus

Denis Duboule, Marion Leleu, Lucille Delisle

BACKGROUND: The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior HoxD g ...

2017

Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster

Denis Duboule

The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxD genes. In rare patients, duplications, balanced translocations or inv ...

NATURE PUBLISHING GROUP2020

Rostral and caudal pharyngeal arches share a common neural crest ground pattern

Denis Duboule

In vertebrates, face and throat structures, such as jaw, hyoid and thyroid cartilages develop from a rostrocaudal metameric series of pharyngeal arches, colonized by cranial neural crest cells (NCCs). Colinear Hox gene expression patterns underlie arch spe ...

2009

A CTCF-dependent mechanism underlies the Hox timer relation to a segmented body plan

Denis Duboule, Hocine Rekaik

During gastrulation, Hox genes are activated in a timesequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated wit ...

Current Biology Ltd2024

Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states

Denis Duboule, Suliana Manley, Aleksandr Benke

Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around th ...

2015

Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids

Matthias Lütolf, Denis Duboule, Mehmet Ugur Girgin, Anne-Catherine Cossy

The emergence of multiple axes is an essential element in the establishment of the mammalian body plan. This process takes place shortly after implantation of the embryo within the uterus and relies on the activity of gene regulatory networks that coordina ...

NATURE PUBLISHING GROUP2018

Genotypic features of lentivirus transgenic mice

Didier Trono, Felix Naef, Denis Duboule, Marc-Olivier Sauvain, Frédéric Schütz

Lentivector-mediated transgenesis is increasingly used, whether for basic studies as an alternative to pronuclear injection of naked DNA or to test candidate gene therapy vectors. In an effort to characterize the genetic features of this approach, we first ...

American Society for Microbiology2008

Hotair Is Dispensible for Mouse Development

Denis Duboule, Anamaria Necsulea

Despite the crucial importance of Hox genes functions during animal development, the mechanisms that control their transcription in time and space are not yet fully understood. In this context, it was proposed that Hotair, a lncRNA transcribed from within ...

Public Library Science2016

Ectopic nuclear reorganisation driven by a Hoxb1 transgene transposed into Hoxd

Denis Duboule

The extent to which the nuclear organisation of a gene impacts on its ability to be expressed, or whether nuclear organisation merely reflects gene expression states, remains an important but unresolved issue. A model system that has been instrumental in i ...

2008

Reorganisation of Hoxd regulatory landscapes during the evolution of a snake-like body plan

Denis Duboule

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 wi ...

Elife Sciences Publications Ltd2016

Uncoupling time and space in the collinear regulation of Hox genes

Denis Duboule

During development of the vertebrate body axis, Hox genes are transcribed sequentially, in both time and space, following their relative positions within their genomic clusters. Analyses of animal genomes support the idea that Hox gene clustering is essent ...

2009

The (unusual) heuristic value of Hox gene clusters; a matter of time?

Denis Duboule

Ever since their first report in 1984, Antennapedia-type homeobox (Hox) genes have been involved in such a series of interesting observations, in particular due to their conserved clustered organization between vertebrates and arthropods, that one may legi ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Tetrapod axial evolution and developmental constraints; Empirical underpinning by a mouse model

Denis Duboule

The tetrapod vertebral column has become increasingly complex during evolution as an adaptation to a terrestrial life. At the same time, the evolution of the vertebral formula became subject to developmental constraints acting on the size of the cervical a ...

Elsevier2015

Context-dependent enhancer function revealed by targeted inter-TAD relocation

Denis Duboule, Lucille Delisle, Guillaume Andrey, Christopher Chase Bolt

Here the authors show that a strong enhancer sequence can be controlled by the chromatin environment provided by a topologically associated domain (TAD) located nearby. An enhancer relocated by homologous recombination takes all the hallmarks of its new ne ...

Nature Portfolio2022

Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Denis Duboule, Guillaume Andrey, Patrick Schorderet

During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood ...

National Academy of Sciences2017

Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos

Denis Duboule, Lucille Delisle, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Célia Corinne Renée Bochaton

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed tr ...

NATURE PORTFOLIO2023