Equipe d’Accueil : Genome Regulation in Cell and Tissue Plasticity
Intitulé de l’Unité : Institut Cochin
Nom du Responsable de l’Unité : Florence NIEDERGANG
Nom du Responsable de l’Équipe : Alexandre MAYRAN / Andrew Oldfield
Adresse : 24 rue du Faubourg Saint Jacques, 75014 Paris
Responsable de l’encadrement : Alexandre MAYRAN
Tél : (33) 01 44 41 23 36 E-mail: alexandre.mayran@inserm.fr
Résumé du projet (environ une demi-page)
Embryonic development emerges from the coordinated activity of thousands of genes that must be activated at the right place and time. This process is controlled by enhancers, regulatory DNA elements that orchestrate gene expression during development. Many developmental genes are controlled by multiple enhancers, yet how these elements cooperate to generate robust developmental programs remains poorly understood. Do enhancers act independently, or do they work together to control cell fate transitions and tissue organization?
Our laboratory addresses this question using gastruloids, stem-cell-derived embryo models that recapitulate key aspects of mammalian gastrulation and body-axis formation. These systems provide a unique opportunity to visualize embryonic self-organization in real time while directly manipulating the regulatory mechanisms that control gene expression. The long-term objective is to establish quantitative rules linking enhancer activity to gene expression and tissue self-organization during development.
As a first step toward this objective, this M2 project will investigate enhancers controlling genes involved in epithelial-to-mesenchymal transition (EMT), a key process during early embryogenesis. Using CRISPR/Cas9 genome engineering, the student will generate fluorescent reporter cell lines to monitor enhancer activity in living cells and during gastruloid development.
The student will validate reporter integration and characterize reporter activity using fluorescence microscopy, live imaging, and flow cytometry. Depending on project progress, selected enhancer perturbations may be performed to evaluate their contribution to gene expression and developmental patterning. These experiments will provide an initial assessment of how enhancer activity contributes to transcriptional regulation during gastruloid development.
The project will provide training in genome engineering, mouse embryonic stem cell culture, gastruloid biology, live imaging, flow cytometry, and quantitative data analysis. The generated tools and datasets will form the basis of a broader research program aimed at understanding how regulatory DNA controls embryonic self-organization.
Dernières Publications en lien avec le projet :
Mayran A#, Kolly D., Lopez-Delisle L., Romaniuk Y, Leonardi M, Cossy AC, Lacroix T, Amândio AR, Osteil P, and Duboule D (# Corresponding Author). (2025) Cell Report
Cadherins modulate the self-organizing potential of pseudo-embryos.
Bennabi I*#, Hansen P*, Merle M, Pineau J, Lopez-Delisle L., Kolly D, Duboule D, Mayran A# and Gregor T#, (*equal contribution, #corresponding authors)
Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudo-embryos. (2025) Science Advances
Rekaik H, Lopez-Delisle L, Hintermann A, Mascrez B, Bochaton C, Mayran A and Duboule D.
Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos, (2023) Nature Genetics
Ce projet s’inscrit dans la perspective d’une thèse
type de financement prévu : Ecole Doctorale, or FRM
Ecole Doctorale de rattachement : BIOSPC ED 562 – BioScience Paris Cité