Cell polarity determinant Dlg1 regulates the spatial organization and contractile behavior of non-muscle myosin II during tissue morphogenesis
Authors: Melisa Fuentes; Bing He
Affiliation: Dartmouth College
Keywords: q. epithelial sheets; b. cell polarity
Contractile forces generated by non-muscle myosin II (“myosin”) are critically involved in many morphogenetic processes in animal development. In this work, we found that the cell polarity determinant Dlg1 regulates the spatial distribution and contractile behavior of myosin during tissue folding and tissue elongation in early Drosophila embryos. During Drosophila gastrulation, ventrally localized mesodermal cells undergo apical constriction and invaginate to form a ventral furrow. We found that depletion of Dlg1 disrupts the transition between apical constriction and invagination without affecting the rate of apical constriction, the main driving force for furrow formation. In Dlg1 deficient embryos, cells adjacent to the constriction domain (“flanking cells”) display a reduced level of apical adherens junctions and ineffective apical myosin contractions. These defects result in overstretching of the apical domain of the flanking cells and weakening of mechanical coupling between the mesoderm and the neighboring ectoderm, which we show is sufficient to cause delay in invagination. After ventral furrow formation, the germband epithelium doubles in length along the anterior-posterior axis by shortening along the dorsal-ventral axis, a process mediated by cell intercalation. During cell intercalation, planar polarized localization of myosin facilitates patterned shrinking of anterior-posterior junctions and extension of dorsal-ventral junctions. We found that loss of Dlg1 in the germband results in a decrease in junctional myosin, an increase in medio-apical myosin, and ectopic accumulation of myosin along the lateral membrane. Further mutant analysis demonstrates that the SH3 and GUK domains of Dlg1 are both important for the proper spatial organization of myosin during germband extension. The myosin regulator Rho-associated kinase (Rok) displays a similar mis-localization pattern as myosin upon loss of Dlg1. These defects are accompanied by ectopic apical constriction in the germband and a reduced rate of tissue extension. Together, our findings reveal the function of Dlg1 in regulating subcellular distribution and/or contractile behavior of myosin in multiple tissues under various developmental contexts.