Tissue swelling and local mechanosensing drive crypt convergence in intestinal development
Year: 2026
Type: preprint
Abstract: 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 reaction to tissue-scale mechanical changes in the surrounding villus. 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 leads instead 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 to local cellular mechanosensation, prevents competitive amplification of variability, coordinating individual units to ensure reproducible tissue architecture.
Source: HAL
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7150381703