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

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

Meeting our Makers: Uncovering the cis-regulatory activity of transposable elements using statistical learning

Cyril David Son-Tuyên Pulver

The adaptation of organisms to their environment depends on the innovative potential inherent to genetic variation. In complex organisms such as mammals, processes like development and immunity require tight gene regulation. Complex forms emerge more often ...

EPFL2024

Wide-scale identification of novel/eliminated genes responsible for evolutionary transformations

Daria Korotkova

BackgroundIt is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid conten ...

2023

Transcriptomic data meta-analysis reveals common and injury model specific gene expression changes in the regenerating zebrafish heart

Marius Alexandru Botos Rogozsan

Zebrafish have the capacity to fully regenerate the heart after an injury, which lies in sharp contrast to the irreversible loss of cardiomyocytes after a myocardial infarction in humans. Transcriptomics analysis has contributed to dissect underlying signa ...

Nature Portfolio2023

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

Statistical learning quantifies transposable element-mediated cis-regulation

Didier Trono, Julien Léonard Duc, Alexandre Coudray, Cyril David Son-Tuyên Pulver, Shaoline Sheppard, Evaristo Jose Planet Letschert, Raphaël Gérard Théodore Michel Marie de Deloÿe et Fourcade de Fondeville, Julien Paul André Pontis, Delphine Yvette L Grun

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

2023

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

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

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

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

The various forms of sensorimotor plasticity following limb amputation and their link with rehabilitation strategies

Estelle Emeline Raffin

Limb amputation is characterized by complex and intermingled brain reorganization processes combining sensorimotor deprivation induced by the loss of the limb per se, and compensatory behaviors, such as the over-use of the intact or remaining limb. While a ...

2021

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

Toward a mechanistic understanding of variable chromatin modules

Gerard Llimos Aubach

Our genome is a long sequence of DNA that contains all the information to be able to constitute a living organism like us, similarly to what the letters in a book do to create a story. This sequence, which is a stretch of molecules called nucleotides, is a ...

EPFL2021

Spontaneous Gait Transitions of Sprawling Quadruped Locomotion by Sensory-Driven Body-Limb Coordination Mechanisms

Auke Ijspeert, Shura Suzuki

Deciphering how quadrupeds coordinate their legs and other body parts, such as the trunk, head, and tail (i.e., body-limb coordination), can provide informative insights to improve legged robot mobility. In this study, we focused on sprawling locomotion of ...

FRONTIERS MEDIA SA2021

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

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

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

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