Uncoupling apical constriction from tissue invagination

Abstract

Apical constriction is a widely utilized cell shape change linked to folding, bending and invagination of polarized epithelia. It remains unclear how apical constriction is regulated spatiotemporally during tissue invagination and how this cellular process contributes to tube formation in different developmental contexts. Using Drosophila salivary gland (SG) invagination as a model, we show that regulation of folded gastrulation expression by the Fork head transcription factor is required for apicomedial accumulation of Rho kinase and non-muscle myosin II, which coordinate apical constriction. We demonstrate that neither loss of spatially coordinated apical constriction nor its complete blockage prevent internalization and tube formation, although such manipulations affect the geometry of invagination. When apical constriction is disrupted, compressing force generated by a tissue-level myosin cable contributes to SG invagination. We demonstrate that fully elongated polarized SGs can form outside the embryo, suggesting that tube formation and elongation are intrinsic properties of the SG.Many organs in the human body – like the kidneys, lungs, and salivary glands – are organized as a single layer of cells that surround a hollow tube. There are a number of ways that cells can achieve this particular arrangement. In one mechanism, a small group of cells bud out of a single cell layer to become the end of a new tube or a new branch of an existing tube. Since all the cells are still connected, the first cells bring their neighbouring cells along behind them, rearranging these cells to form the walls of a tube.In addition to changing position, the cells must change their shape to form a tube. One crucial change in cell shape is called apical constriction, and involves the side of the cell facing the inside of the tube becoming smaller than the other sides. This creates cells with a wedge-like shape that can fit together to form the curved wall of the tube, similar to shaped bricks in an archway. Apical constriction has been widely studied and is controlled by proteins that act like motors moving along protein-based filaments; however the roles of apical constriction in tube formation have not been fully explained.Using the developing salivary glands of the fruit fly Drosophila melanogaster, Chung et al. confirmed that the motor protein known as myosin II controls apical constriction during tissue invagination. Further examination showed that proteins (called Fork Head and Fog) activate and localize an enzyme (Rho kinase) to control the localized accumulation of myosin II and thereby control apical constriction. Chung et al. then showed that salivary glands could still form tubes if apical constriction was blocked, indicating that it is not an essential part of tissue invagination in this organ. However, blocking apical constriction led the tube to develop unusual shapes at intermediate stages.More work is now needed to better understand the links between apical constriction, cell rearrangement and tissue invagination. These processes are fundamental for organs to form correctly in many organisms and understanding their control could have wide-ranging impacts. A better understanding of these processes may provide insight into how the tubes can form while keeping all the cells adequately supplied with oxygen and nutrients, and into diseases that result if there are defects in the invagination process.