Arp2/3-dependent mechanical control of morphogenetic robustness in an inherently challenging environment

Abstract

Summary Epithelial sheets undergo highly reproducible remodeling to shape organs. This stereotyped morphogenesis depends on a well-defined sequence of events leading to the regionalized expression of developmental patterning genes that finally triggers downstream mechanical forces to drive tissue remodeling at a pre-defined position. However, how tissue mechanics controls morphogenetic robustness when challenged by intrinsic perturbations in close proximity has never been addressed. Using Drosophila developing leg, we show that a bias in force propagation ensures stereotyped morphogenesis despite the presence of mechanical noise in the environment. We found that knockdown of the Arp2/3 complex member Arpc5 specifically affects fold directionality while altering neither the developmental nor the force generation patterns. By combining in silico modeling, biophysical tools, and ad hoc genetic tools, our data reveal that junctional myosin II planar polarity favors long-range force channeling and ensures folding robustness, avoiding force scattering and thus isolating the fold domain from surrounding mechanical perturbations.

Different temporal requirements for the LRR transmembrane receptors Tartan and Toll-2 in the formation of contractile interfaces at compartmental boundaries

“…So it is possible that mechanosensitive feedback increase actomyosin enrichment along PSBs, contributing to the real-time responsiveness of boundary formation. This might also contribute to the robustness of boundary formation (Martin et al, 2021).…”

Orchestration of Force Generation and Nuclear Collapse in Apoptotic Cells

“…Several recent works demonstrate that tissue-scale patterns and coupling of the actomyosin cytoskeleton provide robustness during tissue folding [ 69 , 70 , 71 ]. In particular, during leg folding, myosin II is planar polarised at adherens junctions, orienting force propagation along the fold axis.…”

Forced into shape: Mechanical forces in Drosophila development and homeostasis

“…In the Drosophila leg disc, a precise pattern of four parallel folds forms during development and perturbations of Arp2/3 complex component were found to induce deviated folds [137] . Planar polarization of MyoII was shown to be necessary to render the folds insensitive to mechanical perturbation: without it, folds initiate properly but propagate with low precision due to local mechanical noise (e.g.…”

“…Planar polarization of MyoII was shown to be necessary to render the folds insensitive to mechanical perturbation: without it, folds initiate properly but propagate with low precision due to local mechanical noise (e.g. they deviate towards regions of high tension) [137] . The polarization of MyoII ensures that force transmission is biased in the direction of future fold formation, “buffering” the effect of additional forces in the tissue.…”