Myosin II Controls Junction Fluctuations to Guide Epithelial Tissue Ordering

摘要

class="head no_bottom_margin" id="sec1title">IntroductionEpithelia play an important role as selective barriers that separate animal tissues from the external environment. This depends upon the presence of linear adhesive contacts, called adherens junctions (AJs), which bind neighboring cells to one another (, , ). Since epithelia must tolerate changes in cell packing, even during periods of homeostasis, it is important that the loss and gain of AJs occurs without compromising tissue integrity. This requires that AJs be dynamic structures.In a monolayer epithelium, the loss and birth of AJs follows a characteristic trajectory as cells change neighbors. First, an adhesive contact connecting two neighboring epithelial cells is lost, leading to the formation of a four-way vertex. This is then resolved by the birth and elongation of a new AJ interface at ∼90° to the first. This simple process, often called a T1 transition, connects the two cells in a quartet that were previously separate from one another (, , ). Such topological transitions provide epithelial monolayers with the fluidity necessary to preserve tissue integrity in the face of the disruptive influence of epithelial cell division () and cell delamination (); while also allowing packing irregularities and defects in the tissue to be resolved (, ). Moreover, when accompanied by a redistribution of cell mass, directed neighbor exchange events can be used to drive large-scale morphogenetic movements (, ).In many systems, the forces required to drive T1 transitions are generated by the molecular motor, non-muscle Myosin II, as it acts on AJ-associated actin filaments (, ). Through the action of Myosin II, the sliding of anti-parallel filaments, coupled to the AJ, generates localized mechanical tension that causes AJs to shorten, thereby triggering neighbor exchange. This has been especially well studied in the developing Drosophila germband, where polarized junctional actomyosin (), actomyosin flows (href="#bib2" rid="bib2" class=" bibr popnode">Bertet et al., 2004, href="#bib31" rid="bib31" class=" bibr popnode">Rauzi et al., 2010), together with the destabilization of E-cadherin at dorsal-ventral AJs (href="#bib40" rid="bib40" class=" bibr popnode">Tamada et al., 2012) drives tissue elongation (href="#bib3" rid="bib3" class=" bibr popnode">Blankenship et al., 2006, href="#bib21" rid="bib21" class=" bibr popnode">Irvine and Wieschaus, 1994, href="#bib35" rid="bib35" class=" bibr popnode">Simoes Sde et al., 2010). Nevertheless, the impact of actomyosin-based forces on individual AJs and on the tissue as a whole critically depends on the precise localization and polarity of the actomyosin network. Thus, while a pulsed polarized actomyosin network drives neighbor exchange (href="#bib44" rid="bib44" class=" bibr popnode">Zallen and Blankenship, 2008, href="#bib45" rid="bib45" class=" bibr popnode">Zallen and Wieschaus, 2004), medial actomyosin pulses tend to induce apical cell constriction, as seen during ventral furrow invagination (href="#bib25" rid="bib25" class=" bibr popnode">Martin et al., 2009, href="#bib26" rid="bib26" class=" bibr popnode">Mason et al., 2013, href="#bib42" rid="bib42" class=" bibr popnode">Vasquez et al., 2014) and dorsal closure (href="#bib37" rid="bib37" class=" bibr popnode">Solon et al., 2009).Neighbor exchange events have also been suggested to play a much more general role in maintaining the balance between order and disorder in epithelia (href="#bib12" rid="bib12" class=" bibr popnode">Farhadifar et al., 2007, href="#bib24" rid="bib24" class=" bibr popnode">Marinari et al., 2012). However, under conditions of balanced growth or stasis, it is not yet known whether or not actomyosin plays a direct role in the process of neighbor exchange. To address this question, here we utilize the Drosophila pupal notum to explore the regulation and function of junction dynamics in an epithelium during a period in which it remains relatively stable in size and shape (href="#bib4" rid="bib4" class=" bibr popnode">Bosveld et al., 2012, href="#bib17" rid="bib17" class=" bibr popnode">Guirao et al., 2015). Strikingly, in this context, the impact of Myosin-dependent tension on neighbor exchange is different from that described previously. Instead of driving topological rearrangements, junctional actomyosin limits the number of neighbor exchanges in this tissue. This is explained, at least in part, by a computational model, which shows how the variance in actomyosin-based tension across cell-cell junctions over time can determine the impact of junctional actomyosin on tissue topology. Thus, as the levels of junctional Myosin II rise across the tissue over the course of development, the rate of neighbor exchange events declines, aiding the gradual refinement of tissue packing as metamorphosis reaches an end.