Folding mechanisms in two-dimensional cell sheets

Cell sheet folding mediated by apical constriction provides a ubiquitous tissue construction mechanism that converts flat cell sheets into multilayered tissue structures in a variety of developmental contexts. Little is known about how forces produced near the apical surface of the tissue are transmitted within individual cells to generate the global changes in cell shape that underlie tissue deformation. Using Drosophila gastrulation as a model, we recently demonstrated that tissues respond as a viscous continuum to constriction forces generated near the surface of the cell sheet. The resulting viscous flow of the tissue provides a sufficient mechanism to transmit forces deep into the tissue and drive 3D deformation. ImportaEDGE-lengtheningntly, this fluid-like property requires the tissue to be mechanoresponsive, such that the cell membranes expand promptly with the flow without impeding it. While existing models for tissue morphogenesis emphasize the genetic control of force generation, our findings highlight the importance of mechanical properties at both cellular and tissue levels, which up to now have been largely unexplored. Using an interdisciplinary approach combining genetics, cell biology, biophysics and mathematical modeling, we are currently investigating the mechanisms underlying the “expandability” of the cell membrane and the role of mechanical signals in triggering cell membrane expansion and coordination of cell shape changes during cell sheet folding.

Regulation of cortical myosin flow during cellularization

Actomyosin contractility provides a common force generation mechanism in cell and tissue morphogenesis ranging from cytokinesis to cell sheet folding. In Drosophila, the cleavage of the syncytial blastoderm is initiated by an actomyosin network at the base of membrane furrows that invaginate from the surface of the embryo. Our previous work demonstrated that during Drosophila cleavage, myosin recruitment to the cleavage furrows proceeds in temporally distinct phases of tension-driven cortical flow and direct recruitment from the cytoplasm, Myosin flow during cellularizationregulated by different zygotic genes. Both cortical flow and direct recruitment have been previously described in cytokinesis in various organisms, but how they are regulated and coordinated remains unclear. Our results for the first time demonstrate that these mechanisms can be employed at distinct times during a cytokinetic process and separately regulated by transcription. We identified a novel gene dunk, which is specifically transcribed during cellularization and functions to maintain myosin at the cortex during flow-dependent myosin recruitment. The subsequent direct myosin recruitment is Dunk-independent but requires another cellularization protein Slam. These findings establish Drosophila cellularization as an advantageous system to study distinct myosin recruitment mechanisms separately. By investigating the molecular function of Slam and Dunk, we seek to understand how the separate flow and direct recruitment mechanisms can coordinately regulate a morphogenetic process. The identified paradigm may also operate in other actomyosin-dependent processes.