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Epithelial remodeling of the Drosophila retina depends on the pulsatile contraction and expansion of apical contacts between the cells that form its hexagonal lattice. Phosphoinositide PI(3,4,5)P 3 (PIP 3) accumulates around tricellular adherens junctions (tAJs) during contact expansion and dissipates during contraction, but with unknown function. Here, we found that manipulations of Pten or PI3-kinase (PI3K) that either decreased or increased PIP 3 resulted in shortened contacts and a disordered lattice, indicating a requirement for PIP 3 dynamics and turnover. These phenotypes are caused by a loss of branched actin, resulting from impaired activity of the Rac1 Rho GTPase and the WAVE regulatory complex (WRC). We additionally found that during contact expansion, PI3K moves into tAJs to promote the cyclical increase of PIP 3 in a spatially and temporally precise manner. Thus, dynamic control of PIP 3 by Pten and PI3K governs the protrusive phase of junctional remodeling, which is essential for planar epithelial morphogenesis. [Display omitted] • PIP 3 turnover and pulsatile accumulation affect contact length pulsing in eye morphogenesis • PI3K and Pten promote contact expansion by controlling PIP 3 levels and turnover • PIP 3 activates the WAVE regulatory complex, actin branching, and protrusion partially via Rac • PI3K relocates from bAJs to tAJs to expand contacts; Pten is more uniform and diffuse Malin et al. show that PIP 3 turnover and pulsatile accumulation controlled by PI3K and Pten influence the shape and organization of epithelial cells in the Drosophila retina by activating the Rac Rho GTPase, which in turn activates the WAVE regulatory complex, actin branching, and pulsatile contact lengthening. [ABSTRACT FROM AUTHOR]

Abstract We have revised a mathematical model of epithelial morphogenesis by Belintsev et al. (1987) (BB model) taking into account the oscillatory nature of morphogenesis and stability analysis (Cherdantsev, 2014). Following the BB model in considering the feedback control of cell shape changes by mechanical forces, we modify it to represent epithelial surface movements observed in different types of Metazoan gastrulation. Basing on these observations, we argue that the epithelial surface movement is that of an incompressible fluid supplemented by a positive feedback between the movement and spreading of the surface flow. Dipole interactions between sources and sinks of surface energy provide a single mechanism both of short-ranged and long-ranged regulation of collective cell and surface movements whose basic variables are the space averaged epithelial surface curvature and lateral pressure within the epithelial surface flux negatively related to its velocity. The short-ranged activation means a movement of the surface up to the lateral pressure gradient under non-linear feedback control of the surface flexure. The break of this feedback with equalization of the surface curvature is sufficient for a self-restriction of the movement spreading. Owing to bistable interdependence between the lateral pressure and epithelial surface curvature, we get a generic oscillatory contour in which the same region oscillates being alternately a sink and source of the surface flow. The opposite phase oscillations of the lateral pressure and curvature allow for both directional propulsion of the surface through the same region and spatial differentiation based on parametric differences between the large-scaled regions that correspond to sources and sinks of the surface. [ABSTRACT FROM AUTHOR]

In developing embryos, specific cell populations are often removed to remodel tissue architecture for organogenesis. During urinary tract development, an epithelial duct called the common nephric duct (CND) gets shortened and eventually eliminated to remodel the entry point of the ureter into the bladder. Here we show that non-professional efferocytosis (the process in which epithelial cells engulf apoptotic bodies) is the main mechanism that contributes to CND shortening. Combining biological metrics and computational modeling, we show that efferocytosis with actomyosin contractility are essential factors that drive the CND shortening without compromising the ureter-bladder structural connection. The disruption of either apoptosis, non-professional efferocytosis, or actomyosin results in contractile tension reduction and deficient CND shortening. Actomyosin activity helps to maintain tissue architecture while non-professional efferocytosis removes cellular volume. Together our results demonstrate that non-professional efferocytosis with actomyosin contractility are important morphogenetic factors controlling CND morphogenesis. [Display omitted] • Non-professional efferocytosis is the main mechanism for tissue morphogenesis • Mathematical modeling is designed to estimate non-professional efferocytosis timing • Non-professional efferocytosis and actomyosin are essential factors in morphogenetic force Tang et al. show that non-professional efferocytosis is the main mechanism for epithelial duct shortening morphogenesis. Biological metrics and computational modeling suggest the essential roles of non-professional efferocytosis with actomyosin activity to drive duct shortening. Apoptosis, non-professional efferocytosis, and actomyosin all contribute to tension accumulation as crucial morphogenetic factors. [ABSTRACT FROM AUTHOR]

Despite their barrier function, epithelia can locally lose their integrity to create physiological openings during morphogenesis. The mechanisms driving the formation of these epithelial breaks are only starting to be investigated. Here, we study the formation of the zebrafish nostril (the olfactory orifice), which opens in the skin epithelium to expose the olfactory neurons to external odorant cues. Combining live imaging, drug treatments, laser ablation, and tissue-specific functional perturbations, we characterize a mechanical interplay between olfactory placode neurons and the skin, which plays a crucial role in the formation of the orifice: the neurons pull on the overlying skin cells in an actomyosin-dependent manner which, in combination with a local reorganization of the skin epithelium, triggers the opening of the orifice. This work identifies an original mechanism to break an epithelial sheet, in which an adjacent group of cells mechanically assists the epithelium to induce its local rupture. [Display omitted] • The nostril orifice forms in the skin above a rosette of olfactory placode neurons • The orifice opens through the loss of contacts between remodeled skin cells • A cavity in the neuronal rosette center plays an essential role in the opening • Actomyosin-mediated forces from the neurons are required to fully open the orifice The mechanisms driving the physiological opening of epithelial holes remain poorly understood. In this study, Baraban et al. report how the olfactory neurons mechanically contribute to the formation of the zebrafish nostril orifice by pulling on the overlying skin to locally open the epithelium. [ABSTRACT FROM AUTHOR]

Light and electron microscopy were used to compare spider book lung development with earlier studies of the development of horseshoe crab book gills and scorpion book lungs. Histological studies at the beginning of the 20th century provided evidence that spider and scorpion book lungs begin with outgrowth of a few primary lamellae (respiratory furrows, saccules) from the posterior surface of opisthosomal limb buds, reminiscent of the formation of book gills in the horseshoe crab. In spider embryos, light micrographs herein also show small primary lamellae formed at the posterior surface of opisthosomal limb buds. Later, more prominent primary lamellae extend into each book lung sinus from the inner wall of the book lung operculum formed from the limb bud. It appears most primary lamellae continue developing and become part of later book lungs, but there is variation in the rate and sequence of development. Electron micrographs show the process of air channel formation from parallel rows of precursor cells: mode I (cord hollowing), release of secretory vesicles into the extracellular space and mode II (cell hollowing), alignment and fusion of intracellular vesicles. Cell death (cavitation) is much less common but occurs in some places. Results herein support the early 20th century hypotheses that 1) book lungs are derived from book gills and 2) book lungs are an early step in the evolution of spider tracheae. [ABSTRACT FROM AUTHOR]

In apoikogenic scorpions, growing oocytes protrude from the gonad (ovariuterus) and develop in follicles exposed to the mesosomal (i.e. hemocoelic) cavity. During subsequent stages of oogenesis (previtellogenesis and vitellogenesis), the follicles are connected to the gonad surface by prominent somatic stalks. The aim of our study was to analyze the origin, structure and functioning of somatic cells accompanying protruding oocytes. We show that these cells differentiate into two morphologically distinct subpopulations: the follicular cells and stalk cells. The follicular cells gather on the hemocoelic (i.e. facing the hemocoel) surface of the oocyte, where they constitute a cuboidal epithelium. The arrangement of the follicular cells on the oocyte surface is not uniform; moreover, the actin cytoskeleton of these cells undergoes significant modifications during oocyte growth. During initial stages of the stalk formation the stalk cells elongate and form F-actin rich cytoplasmic processes by which the stalk cells are tightly connected to each other. Additionally, the stalk cells develop microvilli directed towards the growing oocyte. Our findings indicate that the follicular cells covering hemocoelic surfaces of the oocyte and the stalk cells represent two distinct subpopulations of epithelial cells, which differ in morphology, behavior and function. [ABSTRACT FROM AUTHOR]

Abstract: Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (purse string) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30s. Circular and elliptical wounds ( in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia. [Copyright &y& Elsevier]

Abstract: The Drosophila leg imaginal disc consists of a peripheral region that contributes to adult body wall, and a central region that forms the leg proper. While the patterning signals and transcription factors that determine the identity of adult structures have been identified, the mechanisms that determine the shape of these structures remain largely unknown. The family of Rho GTPases, which consists of seven members in flies, modulates cell adhesion, actomyosin contractility, protrusive membrane activity, and cell–matrix adhesion to generate mechanical forces that shape adult structures. The Rho GTPases are ubiquitously expressed and it remains unclear how they orchestrate morphogenetic events. The Rho guanine nucleotide exchange factors (RhoGEFs) and Rho GTPase activating proteins (RhoGAPs), which respectively activate and deactivate corresponding Rho GTPases, have been proposed to regulate the activity of Rho signaling cascades in specific spatiotemporal patterns to orchestrate morphogenetic events. Here we identify restricted expression of 12 of the 20 RhoGEFs and 10 of the 22 Rho RhoGAPs encoded in Drosophila during metamorphosis. Expression of a subset of each family of RhoGTPase regulators was restricted to motile cell populations including tendon, muscle, trachea, and peripodial stalk cells. A second subset was restricted either to all presumptive joints or only to presumptive tarsal joints. Depletion of individual RhoGEFs and RhoGAPs in the epithelium of the disc proper identified several joint-specific genes, which act downstream of segmental patterning signals to control epithelial morphogenesis. Our studies provide a framework with which to understand how Rho signaling cascades orchestrate complex morphogenetic events in multi-cellular organisms, and evidence that patterning signals regulate these cascades to control apical constriction and epithelial invagination at presumptive joints. [Copyright &y& Elsevier]

Abstract: The tubular network of the tracheal system in the Drosophila embryo is created from a set of epithelial placodes by cell migration, rearrangements, fusions and shape changes. A designated number of cells is initially allocated to each branch of the system. We show here that the final cell number in the dorsal branches is not only determined by early patterning events and subsequent cell rearrangements but also by elimination of cells from the developing branch. Extruded cells die and are engulfed by macrophages. Our results suggest that the pattern of cell extrusion and death is not hard-wired, but is determined by environmental cues. [Copyright &y& Elsevier]

Abstract: Epithelia are sheets of tightly adherent cells that line both internal and external surfaces in a vast array of metazoans. During development, an intrinsic consequence of coupling tight adhesion with cellular proliferation is the emergence of an epithelial form characterized by a stereotyped distribution of polygonal cell shapes. Despite the near universality of this constraint on cell shape and tissue organization, very little is known about the possible implications of cell pattern geometry for mechanical properties of tissues or key biological processes, such as planar polarization, tissue remodeling, and cell division. In this chapter, through an examination of increasingly complex models, we highlight what is known about the role of mitotic proliferation in the emergence of epithelial cell geometry, and examine some possible implications for tissue morphogenesis. Ideally, continued progress in this area will address a major conceptual challenge in biology, which is to understand aspects of morphogenesis that are not explicitly directed by genetic control, but instead emerge from the complex interactions between geometric and biomechanical properties of epithelial tissues. [Copyright &y& Elsevier]

Cell shape dynamics during development is tightly regulated and coordinated with cell fate determination. Triggered by an interplay between biochemical and mechanical signals, epithelia form complex tissues by undergoing coordinated cell shape changes, but how such spatiotemporal coordination is controlled remains an open question. To dissect biochemical signaling from purely mechanical cues, we developed a microfluidic system that experimentally triggers epithelial folding to recapitulate stereotypic deformations observed in vivo. Using this system, we observe that the apical or basal direction of folding results in strikingly different mechanical states at the fold boundary, where the balance between tissue tension and torque (arising from the imposed curvature) controls the spread of folding-induced calcium waves at a short timescale and induces spatial patterns of gene expression at longer timescales. Our work uncovers that folding-associated gradients of cell shape and their resulting mechanical stresses direct spatially distinct biochemical responses within the monolayer. [Display omitted] • Epithelial polarity defines the arising balance of tension and torque upon folding • Under low tension and increased torque, folding-induced Ca2+ wave spreading is impeded • Direction of folding has differential effects on the local gene expression profile By creating a microsystem to recapitulate in vitro epithelial folds, Blonski et al. show that the direction of folding (apical versus basal) and associated cell shape changes alter the balance locally between tissue tension and torque, which in turn determines the local cellular response to imposed deformation. [ABSTRACT FROM AUTHOR]

Embryos repair wounds rapidly, with no inflammation or scarring, in a process that involves polarization of the actomyosin cytoskeleton. Actomyosin polarization results in the assembly of a contractile cable around the wound that drives wound closure. Here, we demonstrate that a contractile actomyosin cable is not sufficient for rapid wound repair in Drosophila embryos. We show that wounding causes activation of the serine/threonine kinase p38 mitogen-activated protein kinase (MAPK) in the cells adjacent to the wound. p38 activation reduces the levels of wound-induced reactive oxygen species in the cells around the wound, limiting wound size. In addition, p38 promotes an increase in volume in the cells around the wound, thus facilitating the collective cell movements that drive rapid wound healing. Our data indicate that p38 regulates cell volumes through the sodium-potassium-chloride cotransporter NKCC1. Our work reveals cell growth and cell survival as cell behaviors critical for embryonic wound repair. [Display omitted] • p38 MAPK is activated in cells adjacent to wounds in Drosophila embryos • Defective p38 signaling delays wound closure without affecting myosin II dynamics • p38 activation promotes an increase in cell volume that drives rapid wound repair • p38 limits wound size by reducing ROS levels in the cells adjacent to the wound Scepanovic et al. show that cell growth drives rapid embryonic wound healing. Damage-induced activation of p38 in the cells around the wound stimulates the sodium-potassium-chloride cotransporter NKCC1 to promote an increase in cell volume that facilitates tissue repair. p38 also reduces wound-associated oxidative stress, thus limiting wound size. [ABSTRACT FROM AUTHOR]

Abstract: Although epithelial morphogenesis is tightly controlled by intrinsic genetic programs, the microenvironment in which epithelial cells proliferate and differentiate also contributes to the morphogenetic process. The roles of the physical microenvironment in epithelial morphogenesis, however, have not been well dissected. In this study, we assessed the impact of the microenvironment on epithelial cyst formation, which often marks the beginning or end step of morphogenesis of epithelial tissues and the pathological characteristic of some diseases. Previous studies have demonstrated that Madin-Darby canine kidney (MDCK) epithelial cells form cysts when grown in a three-dimensional (3D) extracellullar matrix (ECM) environment. We have now further demonstrated that the presence of ECM in the 3D scaffold is required for the formation of properly polarized cysts. Also, we have found that the full interface of epithelial cells with the ECM environment (in-3D) is not essential for cyst formation, since partial contact (on-3D) is sufficient to induce cystogenesis. In addition, we have defined the minimal ECM environment or the physical threshold for cystogenesis under the on-3D condition. Only above the threshold can the morphological cues from the ECM environment induce cyst formation. Moreover, cyst formation under the on-3D condition described in this study defines a novel and more feasible model to analyze in vitro morphogenesis. Finally, we have found that, during cystogenesis, MDCK cells generate basal microprotrusions and produce vesicle-like structures to the basal extracellular space, which are specific to and correlated with cyst formation. For the first time, we have systematically and quantitatively elucidated the microenvironmental determinants for epithelial cystogenesis. [Copyright &y& Elsevier]

Abstract: Inner ear develops from an induced surface ectoderm placode that invaginates and closes to form the otic vesicle, which then undergoes a complex morphogenetic process to form the membranous labyrinth. Inner ear morphogenesis is severely affected in Gata3 deficient mouse embryos, but the onset and basis of the phenotype has not been known. We show here that Gata3 deficiency leads to severe and unique abnormalities during otic placode invagination. The invagination problems are accompanied often by the formation of a morphological boundary between the dorsal and ventral otic cup and by the precocious appearance of dorsal endolymphatic characteristics. In addition, the endolymphatic domain often detaches from the rest of the otic epithelium during epithelial closure. The expression of several cell adhesion mediating genes is altered in Gata3 deficient ears suggesting that Gata3 controls adhesion and morphogenetic movements in early otic epithelium. Inactivation of Gata3 leads also to a loss of Fgf10 expression in otic epithelium and auditory ganglion demonstrating that Gata3 is an important regulator of Fgf-signalling during otic development. [Copyright &y& Elsevier]

Abstract: The three ERM proteins (Ezrin, Radixin and Moesin) form a conserved family required in many developmental processes involving regulation of the cytoskeleton. In general, the molecular function of ERM proteins is to link specific membrane proteins to the actin cytoskeleton. In Drosophila, loss of moesin (moe) activity causes incorrect localisation of maternal determinants during oogenesis, failures in rhabdomere differentiation in the eye and alterations of epithelial integrity in the wing imaginal disc. Some aspects of Drosophila Moe are related to the activity of the small GTPase RhoA, because the reduction of RhoA activity corrects many phenotypes of moe mutant embryos and imaginal discs. We have analysed the phenotype of moesin loss-of-function alleles in the wing disc and adult wing, and studied the effects of reduced Moesin activity on signalling mediated by the Notch, Decapentaplegic, Wingless and Hedgehog pathways. We found that reductions in Moesin levels in the wing disc cause the formation of wing-tissue vesicles and large thickenings of the vein L3, corresponding to breakdowns of epithelial continuity in the wing base and modifications of Hedgehog signalling in the wing blade, respectively. We did not observe any effect on signalling pathways other than Hedgehog, indicating that the moe defects in epithelial integrity have not generalised effects on cell signalling. The effects of moe mutants on Hedgehog signalling depend on the correct gene-dose of rhoA, suggesting that the requirements for Moesin in disc morphogenesis and Hh signalling in the wing disc are mediated by its regulation of RhoA activity. The mechanism linking Moesin activity with RhoA function and Hedgehog signalling remains to be elucidated. [Copyright &y& Elsevier]

Abstract: The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation. [Copyright &y& Elsevier]

Myosin VI is an unconventional Myosin that has been implicated in vesicle transport and membrane trafficking. We isolated lethal mutants of Myosin VI, which lack protein once maternal supplies have been utilised during embryogenesis. Dorsal closure, where there is a ring of Myosin VI at the edge of the migrating epithelial sheet, is often abnormal. The sheet of migrating cells is irregular, rather than a smooth epithelium and cells begin to detach. Some embryos hatch into larvae, containing detached cells loose in the haemolymph. Myosin VI is crucial for correct cell morphology and maintenance of adhesive cellular contacts within epithelial cell layers. [Copyright &y& Elsevier]

Zona pellucida (ZP) domain proteins have been identified in various species from worms to humans. Most of the characterized ZP family members are secreted or remain anchored to the plasma membrane where they play a structural role and/or act as receptors. In humans, several ZP proteins attracted attention because of their abundant expression in certain organs and their relation to various diseases. Here, we compare the molecular architecture and embryonic expression pattern of the 18 genes encoding ZP proteins in Drosophila melanogaster. Only five of these genes have been genetically characterized. All ZP genes are expressed in the embryo in epithelial tissues, such as the foregut, the hindgut, the Malpighian tubules, the salivary glands, the tracheal system, sensory organs and epidermis. Five genes are expressed during oogenesis; two of them are transcribed in the follicular epithelium, but not in the germ line cells. [Copyright &y& Elsevier]

The elucidation of pathways linking patterning to morphogenesis is a problem of great interest. We show here that, in addition to their roles in patterning and morphogenesis of the hindgut, the Drosophila genes drumstick (drm) and bowl are required in the foregut for spatially localized gene expression and the morphogenetic processes that form the proventriculus. drm and bowl belong to a family of genes encoding C2H2 zinc finger proteins; the other two members of this family are odd-skipped (odd) and sob. In both the fore- and hindgut, drm acts upstream of lines (lin), which encodes a putative transcriptional regulator, and relieves its repressive function. In spite of its phenotypic similarities with drm, bowl was found in both foregut and hindgut to act downstream, rather than upstream, of lin. These results support a hierarchy in which Drm relieves the repressive effect of Lin on Bowl, and Bowl then acts to promote spatially localized expression of genes (particularly the JAK/STAT pathway ligand encoded by upd) that control fore- and hindgut morphogenesis. Since the odd-family and lin are conserved in mosquito, mouse, and humans, we propose that the odd-family genes and lin may also interact to control patterning and morphogenesis in other insects and in vertebrates. [Copyright &y& Elsevier]

Abstract Wound healing in embryos and various developmental events in metazoans require the spreading and fusion of epithelial sheets. The complex signaling pathways regulating these processes are being pieced together through genetic, cell biological, and biochemical approaches. At present, dorsal closure of the Drosophila embryo is the best-characterized example of epithelial sheet movement. Dorsal closure involves migration of the lateral epidermal flanks to close a hole in the dorsal epidermis occupied by an epithelium called the amnioserosa. Detailed genetic studies have revealed a network of interacting signaling molecules regulating this process. At the center of this network is a Jun N-terminal kinase cascade acting at the leading edge of the migrating epidermis that triggers signaling by the TGF-β superfamily member Decapentaplegic and which interacts with the Wingless pathway. These signaling modules regulate the cytoskeletal reorganization and cell shape change necessary to drive dorsal closure. Activation of this network requires signals from the amnioserosa and input from a variety of proteins at cell-cell junctions. The Rho family of small GTPases is also instrumental, both in activation of signaling and regulation of the cytoskeleton. Many of the proteins regulating dorsal closure have been implicated in epithelial movement in other organisms, and dorsal closure has emerged as an ideal model system for the study of the migration and fusion of epithelial sheets. [ABSTRACT FROM AUTHOR]

Toll-like receptors are essential for animal development and survival, with conserved roles in innate immunity, tissue patterning, and cell behavior. The mechanisms by which Toll receptors signal to the nucleus are well characterized, but how Toll receptors generate rapid, localized signals at the cell membrane to produce acute changes in cell polarity and behavior is not known. We show that Drosophila Toll receptors direct epithelial convergent extension by inducing planar-polarized patterns of Src and PI3-kinase (PI3K) activity. Toll receptors target Src activity to specific sites at the membrane, and Src recruits PI3K to the Toll-2 complex through tyrosine phosphorylation of the Toll-2 cytoplasmic domain. Reducing Src or PI3K activity disrupts planar-polarized myosin assembly, cell intercalation, and convergent extension, whereas constitutive Src activity promotes ectopic PI3K and myosin cortical localization. These results demonstrate that Toll receptors direct cell polarity and behavior by locally mobilizing Src and PI3K activity. [Display omitted] • Toll receptors generate planar-polarized patterns of Src and PI3K activity • Src and PI3K are required for localized myosin contractility and convergent extension • Src kinases promote Toll-2 phosphorylation and Toll-2/PI3K-reg complex formation • Toll-2 phosphorylation is necessary for planar polarity and convergent extension Toll receptors provide critical spatial cues that drive cell movements during convergent extension. Tamada and Shi et al. show that Toll receptors organize cell movements by generating planar-polarized patterns of Src and PI3K activity. Toll-2 tyrosine phosphorylation recruits PI3K to the Toll-2 complex, promoting localized myosin assembly and cell rearrangement. [ABSTRACT FROM AUTHOR]

Dynamics of E-cadherin and γ-catenin complexes during dedifferentiation of polarized MDCK cells. Background. E-cadherin mediated cell-cell adhesion and hepatocyte growth factor (HGF) are important for renal epithelial morphogenesis. We previously showed that HGF dedifferentiates previously well polarized Madin-Darby canine kidney (MDCK) cell monolayers grown on filters. The regulation of E-cadherin during epithelial dedifferentiation is not known. We hypothesized that E-cadherin mediated cell-cell adhesion is modulated during HGF induced dedifferentiation of MDCK cell monolayers. Methods. We analyzed E-cadherin/γ-catenin interaction and distribution during epithelial dedifferentiation in vitro using a model of polarized MDCK cell monolayers treated with HGF. Results. Surface immunoprecipitation experiments showed that HGF increased the amount of cell surface E-cadherin associated with γ-catenin. Biochemical and morphological examination of the TX-100 solubility of junctional E-cadherin and γ-catenin in control and HGF treated cells showed an increase in solubility of only E-cadherin during loss of cell polarity. Metabolic labeling of control and HGF treated cells showed that HGF stimulated the synthetic rate of E-cadherin and γ-catenin molecules. Inulin flux across MDCK cell monolayers increases with HGF treatment. Conclusion. These data provide evidence for both the dissociation of E-cadherin molecules from the actin cytoskeleton and an increase in the total number of E-cadherin/γ-catenin complexes on the cell surface during HGF-induced dedifferentiation of polarized renal epithelium. These data support the hypothesis that E-cadherin function is inhibited by a mechanism of detachment from the actin based cytoskeleton during HGF induced dedifferentiation of polarized renal epithelia. [ABSTRACT FROM AUTHOR]

For decades, Drosophila gastrulation has been at the forefront of investigations into the molecular and cell biological principles by which tissues are formed and shaped into organs. Recent work has started to uncover how evolution shaped the elements and the processes of gastrulation during the early divergence of Drosophila and other flies. Here we look at the macroscopic processes that define fly gastrulation and how molecular patterning provides spatial instructions relevant for epithelial remodeling. We integrate studies of gastrulation in other flies to outline how epithelial morphogenesis changed over the course of fly evolution. This work exposes links between morphogenetic differences and changes in molecular patterning and signal transduction. We conclude with a discussion of how gastrulation can evolve through changes in the expression and regulation of patterning genes, or through changes in how such information is relayed to the cytoskeleton. [ABSTRACT FROM AUTHOR]

Epithelial tissues are made of highly specialized cells present in many organs and represent the first barrier of protection from the external environment. Essential for this critical role in protection is their capacity to polarize in the apicobasal axis. The integrity of the epithelium and its properties as a protective barrier is mostly regulated by dynamic intercellular junctions composed of multiprotein complexes. The functionality and dynamics of these junctions are tightly controlled by several signaling processes, including Rho GTPases. Here, we review the most recent data in the contribution of Rho GTPases and their functional regulators during the morphogenesis of epithelial tissues and to maintain the homeostasis in adults. • The integrity of the epithelium is mostly regulated by dynamic junctions. • Intercellular junctions are composed of multiprotein complexes. • Junction functionality and dynamics are tightly controlled by Rho GTPases. • RhoGTPases and their functional regulators in the morphogenesis of epithelial tissue [ABSTRACT FROM AUTHOR]

Summary Contractile forces eliminate cell contacts in many morphogenetic processes. However, mechanisms that balance contractile forces to promote subtler remodeling remain unknown. To address this gap, we investigated remodeling of Drosophila eye lattice cells (LCs), which preserve cell contacts as they narrow to form the edges of a multicellular hexagonal lattice. We found that during narrowing, LC-LC contacts dynamically constrict and expand. Similar to other systems, actomyosin-based contractile forces promote pulses of constriction. Conversely, we found that WAVE-dependent branched F-actin accumulates at LC-LC contacts during expansion and functions to expand the cell apical area, promote shape changes, and prevent elimination of LC-LC contacts. Finally, we found that small Rho GTPases regulate the balance of contractile and protrusive dynamics. These data suggest a mechanism by which WAVE regulatory complex-based F-actin dynamics antagonize contractile forces to regulate cell shape and tissue topology during remodeling and thus contribute to the robustness and precision of the process. [ABSTRACT FROM AUTHOR]