Publication

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

Publications associées (29)

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

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

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

How are cells instructed to form somite boundaries by the zebrafish segmentation clock?

Olivier François Venzin

In vertebrate embryos, the elongating body axis is patterned via the sequential and rhyth-mic production of segments from a posterior unsegmented tissue called the presomitic mesoderm (PSM). This process is controlled by a population of cellular oscillator ...

EPFL2023

Mimicking Loading-Induced Cartilage Self-Heating in Vitro Promotes Matrix Formation in Chondrocyte-Laden Constructs with Different Mechanical Properties

Dominique Pioletti, Naser Nasrollahzadeh Mamaghani, Peyman Karami, Theofanis Stampoultzis, Yanheng Guo

Articular cartilage presents a mechanically sensitive tissue. Chondrocytes, the sole cell type residing in the tissue, perceive and react to physical cues as signals that significantly modulate their behavior. Hyaline cartilage is a connective tissue with ...

2023

Development of a Robotic Microsurgeon for Embryonic Research

Ece Özelçi

Understanding how biological matter takes its shape is instrumental to biology, bioengineering, medicine, and bioinspired engineering. Gaining information on the principles of morphogenesis could enable clinicians to correct developmental abnormalities, ev ...

EPFL2023

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

Premature Vertebral Mineralization in hmx1-Mutant Zebrafish

H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development, and mutations in HMX1 are linked to an ocular defect termed oculoauricular syndrome of Schorderet-Munier-Franceschetti (OAS) (MIM #612109). Recently, additional altered oro ...

2022

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

HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

Alexandre Gauthier Aurèle Mayran

Hox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromat ...

Nature Research2020

Lumbar and thoracic kinematics during step-up: Comparison of three-dimensional angles between patients with chronic low back pain and asymptomatic individuals

Julien Favre, Brigitte Jolles-Haeberli, Guillaume Christe

While alterations in spinal kinematics have been repeatedly observed in patients with chronic low back pain (CLBP), their exact nature is still unknown. Specifically, there is a need for comprehensive assessments of multisegment spinal angles during daily- ...

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

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

In vitro modeling of early mouse development

Mehmet Ugur Girgin

Previous attempts to recapitulate embryogenesis in a developmentally relevant context started with aggregates composed of a few thousand ESCs, termed embryoid bodies (EB), that upon induction of differentiation reveal a surprising level of autonomous cell ...

EPFL2020

Patterning and mechanics of somite boundaries in zebrafish embryos

Andrew Charles Oates, Sundar Ram Naganathan

The body axis of vertebrates is subdivided into repetitive compartments called somites, which give rise primarily to the segmented architecture of the musculoskeletal system in the adult body. Somites form in a sequential and rhythmic manner in embryos and ...

2020

What are you synching about? Emerging complexity of Notch signaling in the segmentation clock

Olivier François Venzin, Andrew Charles Oates

The Segmentation clock is a population of cellular genetic oscillators, located in the posterior of the elongating vertebrate embryo, that governs the rhythmic and sequential segmentation of the body axis into somites. Somites are blocks of cells that give ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2020

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

Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch

The variability in transcription factor concentration among cells is an important developmental determinant, yet how variability is controlled remains poorly understood. Studies of variability have focused predominantly on monitoring mRNA production noise. ...

The Company of Biologists2019

Analysis of long-range gene regulation at the HoxD locus

Ana Rita De Carvalho Amândio Lhopitallier

Hoxd genes are essential for the development of the various body axes in vertebrates and hence the underlying regulatory mechanisms are of paramount importance. Among these various mechanisms are long-range acting enhancers, which are located in the two ad ...

EPFL2019

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