Mundhe, G., Dunsing-Eichenauer, V., Philippe, J.M., Da Silva, , Collinet, C., Lecuit, T. (2026). Spatial patterning of contractility by a self-organized mechanogen activity gradient underlies Drosophila gastrulation.  Nat. Commun. 17(1): 1721.

FBrf0264602

Research paper

During development cell deformations are spatially organized, however, how cellular mechanics is spatially controlled is unclear. Spatial control of cell identity often determines local cellular mechanics in a two-tiered mechanism. Theoretical studies also proposed that molecular gradients, so called "mechanogens", spatially control mechanics. We report evidence of a similar mechanism required for Drosophila gastrulation. We show that the GPCR ligand Fog, expressed in the posterior endoderm, diffuses and acts in a concentration-dependent manner to activate actomyosin contractility at a distance during a wave of tissue invagination. While Fog is uniformly distributed in the extracellular space, it forms a surface-bound gradient that recruits Myosin-II via receptor oligomerization. This activity gradient self-renews as the wave propagates and is shaped by both receptor endocytosis and modulation of GPCR signalling by integrins upon adhesion to the vitelline membrane. This exemplifies how chemical, mechanical and geometrical cues underly the emergence of a self-organized mechanogen activity gradient.

PMC12913813 (PMC) (EuropePMC)