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Concept

Limb development

Related publications (29)

Multi-species atlas resolves an axolotl limb development and regeneration paradox

Can Aztekin, Jixing Zhong, Georgios Tsissios, Evangelia Skoufa

Humans and other tetrapods are considered to require apical-ectodermal-ridge (AER) cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, a primary mode ...

Nature Portfolio2023

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, 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

Premature Vertebral Mineralization in hmx1-Mutant Zebrafish

Daniel Francis Schorderet

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

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

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

Molecular architecture of the developing mouse brain

Gioele La Manno, Irina Khven, Alex Russell Lederer

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of ...

NATURE PORTFOLIO2021

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

TBX3 acts as tissue-specific component of the Wnt/beta-catenin transcriptional complex

Michel Aguet, Andreas Eduard Moor

BCL9 and PYGO are beta-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in de ...

2020

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

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

Spatiotemporal stimulation strategies in neuroprostheses to improve locomotion after spinal cord injury

Jérôme Gandar

Spinal cord injury (SCI) disrupts communication within central nervous system and lead to range of neurological disorders including paralysis. Current rehabilitation strategies to restore locomotion are poorly effective in people with severe SCI. Epidural ...

EPFL2019

Similarities and differences in the regulation of HoxD genes during chick and mouse limb development

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

In all tetrapods examined thus far, the development and patterning of limbs require the activation of gene members of the HoxD cluster. In mammals, they are regulated by a complex bimodal process that controls first the proximal patterning and then the dis ...

PUBLIC LIBRARY SCIENCE2018

Coordinated Hoxd genes expression during embryogenesis is dependent on a strict disposition of genes and polarized regulators within the HoxD cluster

Fabrice Daniel Darbellay

HOX transcription factors determine the identity of body regions along the rostro-caudal axis during bilaterian embryogenesis. In vertebrates Hox genes distinctively lie organized in dense clusters, each typically composed of a dozen paralogous transcripti ...

EPFL2018

Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development

Denis Duboule, Marion Leleu

Background: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation ...

2018

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

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