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Denis Duboule

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

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

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

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 PRESS2019

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

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

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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

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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 ...

BMC2018

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BACKGROUND: The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior HoxD g ...

BioMed Central2017

Control of growth and gut maturation by &ITHoxD&IT genes and the associated lncRNA &ITHaglr&IT

Denis Duboule, Jozsef Zakany, Fabrice Daniel Darbellay, Anamaria Necsulea

During embryonic development, Hox genes participate in the building of a functional digestive system in metazoans, and genetic conditions involving these genes lead to important, sometimes lethal,growth retardation. Recently, this phenotype was obtained af ...

Proceedings of the 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, Pierre Raymond Fabre, Leonardo Beccari, Edgardo Rodriguez Carballo

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 ...

Cold Spring Harbor Laboratory Press2017

Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Denis Duboule, Guillaume Andrey, Patrick Schorderet, Nayuta Yakushiji

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

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with larg ...

Cold Spring Harbor Laboratory Press2017