Bing He Lab

During embryonic development, many morphogenetic changes that form complex tissue and organ structures are driven by remodeling of epithelial tissues, the failure of which can lead to various congenital birth defects. Epithelial morphogenesis is an intrinsically mechanical process dictated by cellular forces and tissue mechanical properties. To date, we have gained extensive knowledge about the genetic regulations of morphogenesis. What remains less clear is the way how these genes coordinately regulate the behavior of cells to generate different tissue forms. Our lab addresses this question by combining genetics, live-embryo-imaging, optogenetics and biophysical approaches. We use Drosophila embryo as our model because of the array of genetic tools available and its easy accessibility for live-imaging and biophysical analyses, which make it an excellent system to study the interplay between genetic activities and tissue mechanics.

Mechanical mechanisms of epithelial folding

Epithelial folding provides a fundamental tissue construction mechanism in embryonic development, a process often mediated by apical constriction. We seek to understand how cells respond to apical constriction to change shape in 3D and how an “in-plane” constriction drives “out-of-the-plane” bending of the tissue.

Drosophila mesoderm invagination (ventral furrow formation)

Bing He Lab

Interplay between intracellular trafficking and tissue mechanics

During tissue morphogenesis, cell shape changes resulting from cell-generated forces often require active regulation of intracellular trafficking. We seek to understand how mechanical stimuli influence intracellular trafficking and how such regulation impacts tissue mechanics.

Dynamics of Rab11 “vesicles” during ventral furrow formation. Top: Rab11 vesicles are transported apical-basally with a strong bias in the apical direction. This bias is quickly abolished upon optogenetics-mediated acute inactivation of actomyosin. Bottom: At the apical side, Rab11 vesicles are targeted to adherens junctions (E-Cadherin) and function to reinforce junction integrity (Chen and He, 2022).

Bing He Lab

Apical-basal polarity, cell-cell adhesion & morphogenesis

Apical basal polarity and cell-cell adhesion are fundamental features of epithelial tissues. We seek to understand how remodeling of cell polarity and adhesion impacts the dynamic remodeling of epithelia during morphogenesis.

The cell polarity determinant Dlg1 facilitates epithelial invagination by promoting tissue-scale mechanical coordination. Left: dlg1 RNAi embryos undergoes apical constriction at a similar rate as the control, but the transition to invagination is delayed. The apical domain of the flanking, non-constricting cells adjacent to the constriction domain are over-stretched in the dlg1 RNAi embryo. Right: Depletion of Dlg1 affects apical myosin (Sqh) contractions in the flanking cells (Fuentes and He, 2022).

Bing He Lab

Optogenetic manipulation of myosin contractility

Actomyosin contractility provides a common force generation mechanism in development. The Opto-Rho1DN optogenetic tool described in our recent work provides an effective approach to acutely disrupt the myosin-dependent force generation machinery.

Optogenetic stimulation of Opto-Rho1DN results in rapid loss of cortical myosin (Sqh) during apical constriction (Guo et al., 2022).

Bing He Lab

Zygotic regulation of cortical myosin during cellularization

Drosophila cellularization is a special form of cleavage that converts syncytial embryos into cellular blastoderms by partitioning the peripherally localized nuclei into individual cells. Similar to canonical animal cytokinesis, cellularization initiates by the recruitment of non-muscle myosin II (“myosin”) to the basal tip of cleavage furrows. We seek to understand how maternal and zygotic gene activities coordinate to regulate cortical myosin during cellularization.

Drosophila cellularization. Top left: membrane (green) invaginate from the surface of the embryo to partition the syncytial nuclei (magenta) into individual cells. Bottom left: 3D rendering of myosin-GFP movie showing a single pair of daughter cells at the beginning of cellularization. Color-coding corresponds to the depth of myosin structures from the apical surface (µm). Right: Comparing basal myosin array in a wild-type embryo and an embryo mutant for the early zygotic gene dunk (He et al., 2016).

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