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Philosophical Transactions of the Royal... Jun 1998The architecture of a tissue is defined by the nature and the integrity of its cellular and extracellular compartments, and is based on proper adhesive cell-cell and... (Review)
Review
The architecture of a tissue is defined by the nature and the integrity of its cellular and extracellular compartments, and is based on proper adhesive cell-cell and cell-extracellular matrix interactions. Cadherins and integrins are major adhesion-mediators that assemble epithelial cells together laterally and attach them basally to a subepithelial basement membrane, respectively. Because cell adhesion complexes are linked to the cytoskeleton and to the cellular signalling pathways, they represent checkpoints for regulation of cell shape and gene expression and thus are instructive for cell behaviour and function. This organization allows a reciprocal flow of mechanical and biochemical information between the cell and its microenvironment, and necessitates that cells actively maintain a state of homeostasis within a given tissue context. The loss of the ability of tumour cells to establish correct adhesive interactions with their microenvironment results in disruption of tissue architecture with often fatal consequences for the host organism. This review discusses the role of cell adhesion in the maintenance of tissue structure and analyses how tissue structure regulates epithelial function.
Topics: Animals; Cell Adhesion; Cytoskeleton; Epithelial Cells; Epithelium; Extracellular Matrix; Homeostasis; Humans; Models, Biological; Signal Transduction
PubMed: 9684283
DOI: 10.1098/rstb.1998.0250 -
PLoS Genetics Jun 2020Forces generated by the actomyosin cytoskeleton are key contributors to many morphogenetic processes. The actomyosin cytoskeleton organises in different types of...
Forces generated by the actomyosin cytoskeleton are key contributors to many morphogenetic processes. The actomyosin cytoskeleton organises in different types of networks depending on intracellular signals and on cell-cell and cell-extracellular matrix (ECM) interactions. However, actomyosin networks are not static and transitions between them have been proposed to drive morphogenesis. Still, little is known about the mechanisms that regulate the dynamics of actomyosin networks during morphogenesis. This work uses the Drosophila follicular epithelium, real-time imaging, laser ablation and quantitative analysis to study the role of integrins on the regulation of basal actomyosin networks organisation and dynamics and the potential contribution of this role to cell shape. We find that elimination of integrins from follicle cells impairs F-actin recruitment to basal medial actomyosin stress fibers. The available F-actin redistributes to the so-called whip-like structures, present at tricellular junctions, and into a new type of actin-rich protrusions that emanate from the basal cortex and project towards the medial region. These F-actin protrusions are dynamic and changes in total protrusion area correlate with periodic cycles of basal myosin accumulation and constriction pulses of the cell membrane. Finally, we find that follicle cells lacking integrin function show increased membrane tension and reduced basal surface. Furthermore, the actin-rich protrusions are responsible for these phenotypes as their elimination in integrin mutant follicle cells rescues both tension and basal surface defects. We thus propose that the role of integrins as regulators of stress fibers plays a key role on controlling epithelial cell shape, as integrin disruption promotes reorganisation into other types of actomyosin networks, in a manner that interferes with proper expansion of epithelial basal surfaces.
Topics: Actomyosin; Animals; Cell Membrane; Cell Shape; Drosophila; Drosophila Proteins; Epithelial Cells; Integrins; Stress Fibers
PubMed: 32479493
DOI: 10.1371/journal.pgen.1008717 -
Cell Adhesion & Migration Dec 2022Laminin 5, type 4 collagen, and α6β4 integrin contribute to the formation of hemidesmosomes in the epithelia of periodontal tissues, which is critical for the...
Laminin 5, type 4 collagen, and α6β4 integrin contribute to the formation of hemidesmosomes in the epithelia of periodontal tissues, which is critical for the development and maintenance of the dentogingival junction. As it is not known whether TNF-α alters the composition of the epithelial pericellular matrix, human gingival epithelial cells were cultured in the presence or absence of TNF-α. Treatment with TNF-α accelerated epithelial cell migration and closure of in vitro wounds. These data indicate unexpectedly, that TNF-α promotes the formation of the pericellular matrix around epithelial cells and enhances adhesion of epithelial cells to the underlying matrix, properties which are important for cell migration and the integrity of the dentogingival junction.
Topics: Basement Membrane; Cell Adhesion; Cell-Matrix Junctions; Epithelial Cells; Humans; Laminin; Tumor Necrosis Factor-alpha
PubMed: 35137648
DOI: 10.1080/19336918.2022.2029237 -
Development (Cambridge, England) Oct 2020Between embryonic days 10.5 and 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei...
Between embryonic days 10.5 and 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei synthesize DNA near the basal surface and move apically to divide. After mitosis, the majority of daughter cells extend a long, basally oriented filopodial protrusion, building a path along which their nuclei can return to the basal side. WNT5A, which is secreted by surrounding mesenchymal cells, acts as a guidance cue to orchestrate this epithelial pathfinding behavior, but how this signal is received by epithelial cells is unknown. Here, we have investigated two known WNT5A receptors: ROR2 and RYK. We found that epithelial ROR2 is dispensable for midgut elongation. However, loss of phenocopies the phenotype, perturbing post-mitotic pathfinding and leading to apoptosis. These studies reveal that the ligand-receptor pair WNT5A-RYK acts as a navigation system to instruct filopodial pathfinding, a process that is crucial for continuous cell cycling to fuel rapid midgut elongation.
Topics: Animals; Apoptosis; Cell Nucleus; Digestive System; Epithelial Cells; Epithelium; Female; Male; Mesoderm; Mice, Inbred C57BL; Pseudopodia; Receptor Protein-Tyrosine Kinases; Receptor Tyrosine Kinase-like Orphan Receptors
PubMed: 32994164
DOI: 10.1242/dev.195388 -
Biochimica Et Biophysica Acta.... Feb 2020Epithelial cells are polarized cells and typically display distinct plasma membrane domains: basal plasma membrane domains face the underlying tissue, lateral domains... (Review)
Review
Epithelial cells are polarized cells and typically display distinct plasma membrane domains: basal plasma membrane domains face the underlying tissue, lateral domains contact adjacent cells and apical domains face the exterior lumen. Each membrane domain is endowed with a specific macromolecular composition that constitutes the functional identity of that domain. Defects in apical-basal plasma membrane polarity altogether or more subtle defects in the composition of either apical or basal plasma membrane domain can give rise to severe diseases. Lipids are the main component of cellular membranes and mechanisms that control their polarized distribution in epithelial cells are emerging. In particular sphingolipids and phosphatidylinositol lipids have taken center stage in the organization of the apical and basolateral plasma membrane domain. This short review article discusses mechanisms that contribute to the polarized distribution of lipids in epithelial cells.
Topics: Animals; Cell Polarity; Endosomes; Epithelial Cells; Humans; Phosphatidylinositols
PubMed: 31809710
DOI: 10.1016/j.bbamem.2019.183145 -
Proceedings of the National Academy of... Aug 2021Multicellular organisms rely on spatial signaling among cells to drive their organization, development, and response to stimuli. Several models have been proposed to...
Multicellular organisms rely on spatial signaling among cells to drive their organization, development, and response to stimuli. Several models have been proposed to capture the behavior of spatial signaling in multicellular systems, but existing approaches fail to capture both the autonomous behavior of single cells and the interactions of a cell with its neighbors simultaneously. We propose a spatiotemporal model of dynamic cell signaling based on Hawkes processes-self-exciting point processes-that model the signaling processes within a cell and spatial couplings between cells. With this cellular point process (CPP), we capture both the single-cell pathway activation rate and the magnitude and duration of signaling between cells relative to their spatial location. Furthermore, our model captures tissues composed of heterogeneous cell types with different bursting rates and signaling behaviors across multiple signaling proteins. We apply our model to epithelial cell systems that exhibit a range of autonomous and spatial signaling behaviors basally and under pharmacological exposure. Our model identifies known drug-induced signaling deficits, characterizes signaling changes across a wound front, and generalizes to multichannel observations.
Topics: Animals; Dipeptides; Dogs; Epithelial Cells; Hydroxamic Acids; Keratinocytes; MAP Kinase Signaling System; Madin Darby Canine Kidney Cells; Mice, Inbred Strains; Mice, Transgenic; Models, Biological; Models, Statistical; Protein Kinase Inhibitors; Signal Transduction; Spatio-Temporal Analysis; Mice
PubMed: 34362843
DOI: 10.1073/pnas.2026123118 -
International Journal of Molecular... Jul 2021Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and causes remodeling of the small airways. However, the exact smoke-induced effects on...
Cigarette Smoke Specifically Affects Small Airway Epithelial Cell Populations and Triggers the Expansion of Inflammatory and Squamous Differentiation Associated Basal Cells.
Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and causes remodeling of the small airways. However, the exact smoke-induced effects on the different types of small airway epithelial cells (SAECs) are poorly understood. Here, using air-liquid interface (ALI) cultures, single-cell RNA-sequencing reveals previously unrecognized transcriptional heterogeneity within the small airway epithelium and cell type-specific effects upon acute and chronic cigarette smoke exposure. Smoke triggers detoxification and inflammatory responses and aberrantly activates and alters basal cell differentiation. This results in an increase of inflammatory basal-to-secretory cell intermediates and, particularly after chronic smoke exposure, a massive expansion of a rare inflammatory and squamous metaplasia associated basal cell state and an altered secretory cell landscape. ALI cultures originating from healthy non-smokers and COPD smokers show similar responses to cigarette smoke exposure, although an increased pro-inflammatory profile is conserved in the latter. Taken together, the in vitro models provide high-resolution insights into the smoke-induced remodeling of the small airways resembling the pathological processes in COPD airways. The data may also help to better understand other lung diseases including COVID-19, as the data reflect the smoke-dependent variable induction of SARS-CoV-2 entry factors across SAEC populations.
Topics: Airway Remodeling; Alveolar Epithelial Cells; Cell Differentiation; Cells, Cultured; Cigarette Smoking; Epithelial Cells; Humans; Neoplasms, Basal Cell; Primary Cell Culture; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Smoke; Smoking
PubMed: 34299265
DOI: 10.3390/ijms22147646 -
Neuron Sep 2010Interkinetic nuclear migration (INM), the movement of neuroepithelial and radial glial cell nuclei along the apical-basal axis in concert with the cell cycle, underlies... (Review)
Review
Interkinetic nuclear migration (INM), the movement of neuroepithelial and radial glial cell nuclei along the apical-basal axis in concert with the cell cycle, underlies the pseudostratification of the ventricular zone (VZ). Recent studies provide insight into the molecular mechanisms of INM and its effects on neural progenitor cell fate determination. Moreover, INM not only has a key role in increasing the VZ progenitor pool, but also may have set the stage for the evolution of subventricular zone progenitors implicated in cortical expansion.
Topics: Actomyosin; Animals; Cell Cycle; Cell Differentiation; Cell Nucleus; Cell Polarity; Centrosome; Cerebral Ventricles; Humans; Microtubules; Neurons; Stem Cells
PubMed: 20869589
DOI: 10.1016/j.neuron.2010.08.027 -
Clinical and Translational Science Oct 2011Enteroendocrine cells (EECs) play a key role in nutrient digestion and absorption, and are essential for normal life. Recently, EEC function has received considerable... (Review)
Review
Enteroendocrine cells (EECs) play a key role in nutrient digestion and absorption, and are essential for normal life. Recently, EEC function has received considerable attention because several gastrointestinal hormones modulate insulin secretion and food intake; and, gut hormone-based therapies have been developed to treat diabetes mellitus. Despite these advances, the regulation of EECs remains poorly understood. The development of transgenic mouse models that express green fluorescent proteins (GFP) under specific hormone promoters (e.g., peptide YY-GFP) is shedding light onto previously overlooked features of EECs. These cells have prominent cytoplasmic processes that extend underneath enterocytes, and in some EECs, such as the L cell of the distal ileum, the basal process can be over 50 μm long. These basal cytoplasmic processes resemble axons and end in synaptic-like bouton. The location and anatomy of these processes suggest two functions: (1) to monitor absorbed nutrients at the base of enterocytes; and (2) to convey electrochemical information through cell-cell connections with subepithelial myofibroblasts and/or nerves located directly beneath in the lamina propria. Understanding how EECs communicate with cells in the lamina propria may provide novel ways to treat metabolic disorders such as obesity and diabetes.
Topics: Animals; Axons; Bacteria; Enteroendocrine Cells; Humans; Signal Transduction
PubMed: 22029814
DOI: 10.1111/j.1752-8062.2011.00299.x -
Cell Structure and Function Oct 2016Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell... (Review)
Review
Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell with their minus ends oriented towards the apical pole. Although this unique orientation of microtubules was discovered in the late 1980s, how this orientation is established remains unresolved partly because of limited information about molecular factors that regulate the minus ends of non-centrosomal microtubules. Recent studies, however, identified novel minus end-associated proteins, revealing mechanisms by which the polarized arrays of microtubules are established in epithelial cells. These studies have also demonstrated the importance of apico-basally orientated microtubules in intra-structural organization of cells. This review focuses on recent progress of our understanding of the molecular basis for epithelium-specific microtubule assembly and function.
Topics: Animals; Epithelium; Intercellular Junctions; Microtubule-Associated Proteins; Microtubules; Models, Molecular
PubMed: 27615606
DOI: 10.1247/csf.16015