Actomyosin-based tissue folding requires a multicellular myosin gradient

Abstract

Tissue folding promotes three-dimensional (3D) form during development. In many cases, folding is associated with myosin accumulation at the apical surface of epithelial cells, as seen in the vertebrate neural tube and the Drosophila ventral furrow. This type of folding is characterized by constriction of apical cell surfaces, and the resulting cell shape change is thought to cause tissue folding. Here, we use quantitative microscopy to measure the pattern of transcription, signaling, myosin activation and cell shape in the Drosophila mesoderm. We found that cells within the ventral domain accumulate different amounts of active apical non-muscle myosin 2 depending on the distance from the ventral midline. This gradient in active myosin depends on a newly quantified gradient in upstream signaling proteins. A 3D continuum model of the embryo with induced contractility demonstrates that contractility gradients, but not contractility per se, promote changes to surface curvature and folding. As predicted by the model, experimental broadening of the myosin domain in vivo disrupts tissue curvature where myosin is uniform. Our data argue that apical contractility gradients are important for tissue folding.

Mechanical feedback and robustness of apical constrictions inDrosophilaembryo ventral furrow formation

“…These constrictions are typically anisotropic, resulting in the minor axis undergoing the most pronounced changes. This behavior is consistent with the dorsal-ventral (ventral-lateral) bias in apical constriction previously observed [27,28].…”

In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition

“…Results above identify two distinct migratory mechanisms, one arising from pEMT and the other from UJT. To better understand underlying mechanical factors that differentiate pEMT versus UJT, we extend previous computational analyses based on so-called vertex models 37,39,91,92,[109][110][111][112] . This extended model is described in detail in the Supplementary Methods and is referred to here as the dynamic vertex model (DVM).…”

Dynamics of Spaetzle morphogen shuttling in theDrosophilaembryo shapes pattern

“…This appears to be the case for T48, which encodes a transmembrane protein that 368 facilitates recruitment of RhoGEF2 and ultimately Rho and actomyosin, to mediate apical 369 constriction of invaginating mesodermal cells (Kolsch et al, 2007). Graded distribution of 370 myosin II was shown to be critical for proper invagination of these cells to form the ventral 371 furrow (Heer et al, 2017). 372…”

“…232 the zygotic target genes twist (twi) and snail (sna) (Rusch and Levine, 1996). However, a 248 graded zygotic response within the mesoderm is also required: A gradient of apical myosin II 249 recruitment, peaking at the ventral midline, is essential for the ordered apical cell constriction 250 driving ventral furrow formation (Heer et al, 2017). A zygotic target gene that may lead to 251 graded myosin II distribution is T48, since the T48 protein recruits Rho GEF2 to the apical 252 membrane, triggering the accumulation and contractile activity of an apical actomyosin 253 network (Kolsch et al, 2007).…”