Vertebrate organogenesis

Participants: Nicolas Chevalier, Monique Frain, Nadine Peyrieras, Thierry Savy

Organogenesis and mechanobiology of the intestine

We are studying the morphogenesis of the intestine and its motility (peristalsis) in avian and murine models. We have identified two biomechanical mechanisms responsible for the anisotropic growth of the intestine and its enteric nervous system during embryonic development, which largely explain the pathogenesis of Short Bowel Syndrome. We have studied in detail the developmental sequence of peristalsis leading from purely muscular contractions mediated by calcium waves, to contractions triggered by pacemaker cells (interstitial cells of Cajal), and finally to the control of motility by the enteric nervous system, giving rise to a mechanosensitive rostro-caudal polarity and a new type of digestive wave (the migrating motor complex). We have simulated and experimentally verified hydrodynamic flows in the lumen of the intestine under the effect of its contractions; we are currently studying the mechano-electrical coupling of the intestinal nervous system in a genetic mouse model fluorescing for calcium events in the enteric nervous system. In mammals, we have demonstrated an orientation phase transition of neural crest cells (precursors of the enteric nervous system) in the developing intestine, mediated by adhesion of these cells to the extracellular collagen matrix secreted by smooth muscle.

Morphogenesis and wound healing in zebrafish

The arrival of the biologists in the team is concomitant with the completion of the two theses in the ImageInLife 2017-2021 ITN focusing respectively on “multiscale dynamics in the morphogenesis of the rhombencephalon in zebrafish” (Mageshi Kamaraj, direction Monique Frain) and “Multiscale dynamics during gastrulation of the zebrafish embryo and embryoid” (Svetlana Jovanic, direction Nadine Peyriéras, co-direction Thierry Savy). Svetlana Jovanic’s thesis work could find a follow-up in the ERC synergy project HETEROMORPH led by A. Sarti and submitted in 2022.
Saatvik Potluri’s current thesis [European contract ITN INFLANET (2021-2025)] focuses on the urokinase pathway and extracellular matrix remodeling in experimental models of inflammation in zebrafish (supervisor Nadine Peyriéras, co-supervisors Monique Frain and Thierry Savy). Since arriving at MSC, the student has established a model of inflammation in larval zebrafish based on caudal fin ablation. A tool for sectioning under the microscope has been developed. The cutting operation will be robotized. Conditions for 3D+time multiphoton microscopy observation and monitoring of mobilized cells at the wound site have been established. Molecular tools for labelling the extracellular matrix and components of the Urokinase pathway have been developed and validated.

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