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Tissue swelling and local mechanosensing drive crypt convergence in intestinal development

30 July - 10h00 - 23h59

Centre de recherche - Paris

Amphithéâtre Hélène Martel-Massignac (BDD)

11 rue Pierre et Marie Curie - 75005 Paris

Description

During development, organs acquire their function by assembling repeating structural units into coherent architectures. While the formation of individual units from cellular processes is increasingly well characterized, how neighbouring units coordinate their growth to achieve reproducible tissue organization remains unclear. Here, we focus on the mouse intestine, where thousands of stem-cell-rich crypts form postnatally with initially highly variable morphologies. Combining in vivo developmental time courses, organoids, and biophysical modelling, we find that crypts rapidly converge morphologically in response to tissue-scale mechanical changes in the surrounding villi. We show that transient swelling of villus enterocytes relaxes epithelial tension and increases crypt cell density. This density increase activates a mechanosensitive pathway in stem cells, in which the cytosolic calcium-dependent phospholipase cPLA2 promotes apical myosin relocalization. This process synchronizes apical contractility across neighbouring crypts, driving their morphological convergence. Disruption of either pathway instead leads to winner-takes-all dynamics, where only the initially more mature crypts close, at the expense of the others. Together, these findings identify a general principle of morphogenesis in which a global mechanical context, coupled with local cellular mechanosensation, prevents competitive amplification of variability and coordinates individual units to ensure reproducible tissue architecture.

Speakers

Laura CAPOLUPO

Friedrich Miescher Institute, Bâle

Invited by

Jean-Léon MAÎTRE

Institut Curie

A question about the seminar?

Jean-Léon MAÎTRE

Jean-Leon.Maitre@curie.fr