@article {49735, title = {Quantitative 4D analyses of epithelial folding during Drosophila gastrulation.}, journal = {Development}, volume = {141}, year = {2014}, month = {2014 Jul}, pages = {2895-900}, abstract = {

Understanding the cellular and mechanical processes that underlie the shape changes of individual cells and their collective behaviors in a tissue during dynamic and complex morphogenetic events is currently one of the major frontiers in developmental biology. The advent of high-speed time-lapse microscopy and its use in monitoring the cellular events in fluorescently labeled developing organisms demonstrate tremendous promise in establishing detailed descriptions of these events and could potentially provide a foundation for subsequent hypothesis-driven research strategies. However, obtaining quantitative measurements of dynamic shapes and behaviors of cells and tissues in a rapidly developing metazoan embryo using time-lapse 3D microscopy remains technically challenging, with the main hurdle being the shortage of robust imaging processing and analysis tools. We have developed EDGE4D, a software tool for segmenting and tracking membrane-labeled cells using multi-photon microscopy data. Our results demonstrate that EDGE4D enables quantification of the dynamics of cell shape changes, cell interfaces and neighbor relations at single-cell resolution during a complex epithelial folding event in the early Drosophila embryo. We expect this tool to be broadly useful for the analysis of epithelial cell geometries and movements in a wide variety of developmental contexts.

}, keywords = {Animals, Body Patterning, Cell Shape, Cell Tracking, Drosophila melanogaster, Epithelial Cells, Epithelium, Gastrulation, Image Processing, Computer-Assisted, software}, issn = {1477-9129}, doi = {10.1242/dev.107730}, author = {Khan, Zia and Wang, Yu-Chiun and Wieschaus, Eric F and Kaschube, Matthias} } @article {49739, title = {Distinct Rap1 activity states control the extent of epithelial invagination via α-catenin.}, journal = {Dev Cell}, volume = {25}, year = {2013}, month = {2013 May 13}, pages = {299-309}, abstract = {

Localized cell shape change initiates epithelial folding, while neighboring cell invagination determines the final depth of an epithelial fold. The mechanism that controls the extent of invagination remains unknown. During Drosophila gastrulation, a higher number of cells undergo invagination to form the deep posterior dorsal fold, whereas far fewer cells become incorporated into the initially very similar anterior dorsal fold. We find that a decrease in α-catenin activity causes the anterior fold to invaginate as extensively as the posterior fold. In contrast, constitutive activation of the small GTPase Rap1 restricts invagination of both dorsal folds in an α-catenin-dependent manner. Rap1 activity appears spatially modulated by Rapgap1, whose expression levels are high in the cells that flank the posterior fold but low in the anterior fold. We propose a model whereby distinct activity states of Rap1 modulate α-catenin-dependent coupling between junctions and actin to control the extent of epithelial invagination.

}, keywords = {Actins, alpha Catenin, Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Membrane, Cell Shape, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, Enzyme Activation, Epithelial Cells, Genes, Insect, Green Fluorescent Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins, Intercellular Junctions, RNA Interference, Time factors, Time-Lapse Imaging}, issn = {1878-1551}, doi = {10.1016/j.devcel.2013.04.002}, author = {Wang, Yu-Chiun and Khan, Zia and Wieschaus, Eric F} } @article {49742, title = {Differential positioning of adherens junctions is associated with initiation of epithelial folding.}, journal = {Nature}, volume = {484}, year = {2012}, month = {2012 Apr 19}, pages = {390-3}, abstract = {

During tissue morphogenesis, simple epithelial sheets undergo folding to form complex structures. The prevailing model underlying epithelial folding involves cell shape changes driven by myosin-dependent apical constriction. Here we describe an alternative mechanism that requires differential positioning of adherens junctions controlled by modulation of epithelial apical-basal polarity. Using live embryo imaging, we show that before the initiation of dorsal transverse folds during Drosophila gastrulation, adherens junctions shift basally in the initiating cells, but maintain their original subapical positioning in the neighbouring cells. Junctional positioning in the dorsal epithelium depends on the polarity proteins Bazooka and Par-1. In particular, the basal shift that occurs in the initiating cells is associated with a progressive decrease in Par-1 levels. We show that uniform reduction of the activity of Bazooka or Par-1 results in uniform apical or lateral positioning of junctions and in each case dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par-1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions not only alters the apical shape of the initiating cells, but also forces the lateral membrane of the adjacent cells to bend towards the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.

}, keywords = {Adherens Junctions, Animals, Cell Polarity, Cell Shape, Choristoma, Drosophila melanogaster, Drosophila Proteins, Epithelial Cells, Epithelium, Gastrula, Gastrulation, Glycogen Synthase Kinase 3, Intracellular Signaling Peptides and Proteins, Protein-Serine-Threonine Kinases}, issn = {1476-4687}, doi = {10.1038/nature10938}, author = {Wang, Yu-Chiun and Khan, Zia and Kaschube, Matthias and Wieschaus, Eric F} }