Description du projet
Un système basé sur les cellules souches permet d’étudier le plan du schéma corporel des mammifères
Le développement des tissus et organes embryonnaires nécessite la mise en place de trois axes orthogonaux fournissant une référence pour le schéma corporel. L’analyse génétique de ce processus suggère un plan transcriptionnel sous-jacent qui relie le système de coordonnées et le schéma corporel. Le projet MiniEmbryoBlueprint, financé par l’UE, aura recours à un système de gastruloïdes basé sur des cellules souches pluripotentes pour mieux comprendre les mécanismes associés à l’émergence du schéma corporel des mammifères. Les gastruloïdes s’organisent à la manière d’un embryon de souris à mi-gestation en cinq jours. La recherche exploite la polyvalence expérimentale du système de gastruloïdes pour étudier les relations entre les activités mécaniques des ensembles multicellulaires et la dynamique génétique qui sous-tend l’émergence du schéma corporel des mammifères.
Objectif
The development of an embryo requires the spatially structured emergence of tissues and organs. This process relies on the early establishment of a coordinate system in the form of three orthogonal axes that act as a reference for laying down the body plan, a template for the organism. Genetic analysis of this process has revealed an underlying transcriptional blueprint that links the coordinate system and the body plan. However, the way in which the gene products contribute to the emergence of the body plan remains an open question. A reason for this is that this process involves feedbacks and integration between the activity of Gene Regulatory Networks (GRNs) and the mechanics of multicellular ensembles, and that probing this relationship is experimentally challenging. In the case of mammalian embryos, which are particularly important as models for human development, our gaps in knowledge of these events are larger than in other organisms. This is partly due to the challenges associated with uterine development but also, and increasingly, because of the cost of mice and the difficulty of obtaining large numbers of embryos, as required for mechanistic experiments. In this project we shall use gastruloids, a novel and versatile Pluripotent Stem Cells based experimental system that we have developed for the study of mammalian development, to gain insights into the molecular and cellular basis underlying the emergence of the mammalian body plan. Gastruloids lack anterior neural structures and over a period of five days become organized in the fashion of a midgestation mouse embryo. We shall use the experimental versatility of the Gastruloid system to probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics of GRNs that underlie the emergence of the mammalian body plan.
Champ scientifique
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ERC-ADG - Advanced GrantInstitution d’accueil
08002 Barcelona
Espagne