Publications de Denis Duboule | EPFL Graph Search

Comments on the Hox timer and related issues

In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years ...

2025

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

Denis Duboule, Lucille Delisle, Alexandre Gauthier Aurèle Mayran

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

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

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

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

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

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

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

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

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

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

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

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

Denis Duboule, Christopher Chase Bolt, Lucille Delisle

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

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

Denis Duboule, Leonardo Beccari, Lucille Delisle, Jozsef Zakany

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

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

Denis Duboule, Marie-Laure Gadolini, Christopher Chase Bolt, Lucille Delisle, Edgardo Rodriguez Carballo

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, Aurélie Hintermann, Jozsef Zakany

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

Chromatin topology and the timing of enhancer function at the HoxD locus

Denis Duboule, Leonardo Beccari, Lucille Delisle, Edgardo Rodriguez Carballo

The HoxD gene cluster is critical for proper limb formation in tetrapods. In the emerging limb buds, different subgroups of Hoxd genes respond first to a proximal regulatory signal, then to a distal signal that organizes digits. These two regulations are e ...

National Academy of Sciences2020

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

Denis Duboule, Christopher Chase Bolt, Lucille Delisle

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

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

Tail Bud Progenitor Activity Relies on a Network Comprising Gdf11, Lin28, and Hox13 Genes

Denis Duboule

During 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 ...

Cell Press - Elsevier2019

Constrained Transcriptional Polarity In The Organization Of Mammalian Hox Gene Clusters

Denis Duboule, Saskia Joëlle Delpretti Anex, Célia Corinne Renée Bochaton, Fabrice Daniel Darbellay, Lucille Delisle, Jozsef Zakany

2019

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

Denis Duboule, Nayuta Yakushiji, Lucille Delisle, Edgardo Rodriguez Carballo

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

Commentary on paper by Leroy C. Stevens (1960)

Denis Duboule

ACADEMIC PRESS INC ELSEVIER SCIENCE2019

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

Matthias Lütolf, Denis Duboule, Leonardo Beccari, Mehmet Ugur Girgin, Anne-Catherine Cossy, Alfonso Martinez Arias

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

Noncoding copy-number variations are associated with congenital limb malformation

Denis Duboule

2018