Mechanical bistability of the mesoderm facilitates mesoderm invagination during Drosophila gastrulation
Authors: Hanqing Guo 1; Michael Swan 2; Bing He 1
Affiliations: 1) Dartmouth College; 2) Princeton University
Keywords: q. epithelial sheets; a. cytoskeleton
Apical constriction driven by non-muscle myosin II (“myosin”) provides a well-conserved mechanism to mediate epithelial folding. It remains unclear how contractile forces near the apical surface of a cell sheet drive out-of-plane bending of the sheet and whether myosin contractility is required throughout folding. We developed a CRY2-CIB based optogenetic system (“Opto-Rho1DN”) to inhibit the myosin activator Rho1 during Drosophila mesoderm invagination, a typical epithelial folding process mediated by apical constriction. Stimulation of Opto-Rho1DN resulted in rapid myosin dissociation from the cell cortex and disassembly of apical actin, causing acute loss of actomyosin contractility. Interestingly, we find that inhibition of actomyosin contractility during the early, “priming” stage of invagination causes reversal of invagination (the “Early group”). In contrast, invagination continues when inhibition is imposed during the actual folding step after the tissue passes through a stereotyped transitional configuration (the “Late group”). This binary response to actomyosin inhibition suggests that the mesoderm is mechanically bistable during gastrulation. Through 3D reconstitution, we show that apical relaxation happens in both groups after stimulation but has distinct impact on cells that have bent towards the ventral midline due to apical constriction. In the Early group, the bent cells unbend. In the Late group, however, the bent cells keep bending towards the ventral midline as invagination continues, suggesting the presence of additional mechanical input other than actomyosin contractility. Computer modeling suggests that the observed mechanical bistability can arise from an in-plane compression from the surrounding ectoderm, analogous to a buckling process. In line with this model, we find that the transitional state coincides with an apical-basal cell shortening in ectoderm, which may generate in-plane compression through cell volume conservation. Importantly, ectodermal shortening still occurs in the absence of apical constriction, indicating that they can provide distinct mechanical input for mesoderm folding. Taken together, our results demonstrate mechanical bistability in Drosophila mesoderm during gastrulation and suggest that mesoderm invagination is mediated by a joint action of local apical contractility and global tissue compression to trigger epithelial buckling.