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

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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

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

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

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

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

Beyond undulation! Body morphology and sensing components of elongated animals and robots reveal skills to maintain competent locomotion

Laura Isabel Paez Coy

Locomotion is an essential evolutive innovation of living beings that allows them to colonize and dominate the planet. As diverse as animal morphologies are (living) and were (extinct), their locomotion modalities are also diverse. In particular, animal mo ...

EPFL2023

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

Hunting for the wavefront: investigation of somite boundary positioning in zebrafish

Arianne Bercowsky Rama

Somitogenesis is the rhythmic and sequential formation of somites, which are tissue blocks that give rise to segmented adult body structures including the vertebrae and associated muscle. Somite formation is controlled by the segmentation clock, a populati ...

EPFL2022

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

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

The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benjamin Marcel Daniel Rothé

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic inte ...

Nature Research2021

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

Auke Ijspeert

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

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, Lucille Delisle

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

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

Amphibious and Sprawling Locomotion: From Biology to Robotics and Back

Auke Ijspeert

A milestone in vertebrate evolution, the transition from water to land, owes its success to the development of a sprawling body plan that enabled an amphibious lifestyle. The body, originally adapted for swimming, evolved to benefit from limbs that enhance ...

2020

Inter-embryo gene expression variability recapitulates the hourglass pattern of evo-devo

Bart Deplancke, Vincent Roland Julien Gardeux, Michael Vincent Frochaux

Background The evolution of embryological development has long been characterized by deep conservation. In animal development, the phylotypic stage in mid-embryogenesis is more conserved than either early or late stages among species within the same phylum ...

2020

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

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

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