Spatial patterning of contractility by a mechanogen gradient underlies Drosophila gastrulation

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 ( 1 ). Theoretical studies also proposed that molecular gradients, so called “mechanogens”, spatially control mechanics ( 2, 3 ). We report evidence of such a “mechanogen” required for Drosophila gastrulation. We show that the GPCR ligand Fog, expressed in the posterior endoderm ( 4–6 ), 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 activates Myosin-II via receptor oligomerization. This activity gradient self-renews as the wave propagates and is shaped by both receptor endocytosis and a feedback mechanism involving adhesion to the vitelline membrane by integrins. This exemplifies how chemical, mechanical and geometrical cues underly the emergence of a self-organized mechanogen activity gradient.