scholarly journals Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis

2008 ◽  
Vol 183 (4) ◽  
pp. 625-633 ◽  
Author(s):  
Aron B. Jaffe ◽  
Noriko Kaji ◽  
Joanne Durgan ◽  
Alan Hall
Keyword(s):  
Cell Division ◽  
Epithelial Cell ◽  
Three Dimensional ◽  
Epithelial Morphogenesis ◽  
Spindle Orientation ◽  
Epithelial Cell Line ◽  
Epithelial Tissue ◽  
Apical Surface ◽  
Apical Domain ◽  
Underlying Mechanisms

The establishment of apical–basal polarity within a single cell and throughout a growing tissue is a key feature of epithelial morphogenesis. To examine the underlying mechanisms, the human intestinal epithelial cell line Caco-2 was grown in a three-dimensional matrix to generate a cystlike structure, where the apical surface of each epithelial cell faces a fluid-filled central lumen. A discrete apical domain is established as early as the first cell division and between the two daughter cells. During subsequent cell divisions, the apical domain of each daughter cell is maintained at the center of the growing structure through a combination of mitotic spindle orientation and asymmetric abscission. Depletion of Cdc42 does not prevent the establishment of apical–basal polarity in individual cells but rather disrupts spindle orientation, leading to inappropriate positioning of apical surfaces within the cyst. We conclude that Cdc42 regulates epithelial tissue morphogenesis by controlling spindle orientation during cell division.

scholarly journals Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon

2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata
Keyword(s):  
Progenitor Cells ◽  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Neural Progenitor ◽  
Hippo Signaling ◽  
Apical Surface ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

2005 ◽  
Vol 288 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Jiing Chyuan Luo ◽  
Vivian Yvonne Shin ◽  
Ying Hua Yang ◽  
William Ka Kei Wu ◽  
Yi Ni Ye ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Epithelial Cell Line ◽  
Epithelial Cell Proliferation ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Factor Α

TNF-α is a cytokine produced during gastric mucosal injury. We examined whether TNF-α could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-α treatment (1–10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-α treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-α on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-α on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-α plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-α receptor and activation of the arachidonic acid/PG pathway.

scholarly journals LMO7-dependent apical constriction requires the binding of the Myosin heavy chain

2021 ◽  
Author(s):  
Miho Matsuda ◽  
Chih-Wen Chu ◽  
Sergei S Sokol
Keyword(s):  
Heavy Chain ◽  
Myosin Light Chain ◽  
Myosin Ii ◽  
Tube Formation ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Apical Domain ◽  
Underlying Mechanisms ◽  
Muscle Myosin

The reduction of the apical domain, or apical constriction, is a process that occurs in a single cell or is coordinated in a group of cells in the epithelium. Coordinated apical constriction is particularly important when the epithelium is undergoing dynamic morphogenetic events such as furrow or tube formation. However, the underlying mechanisms remain incompletely understood. Here we show that Lim only protein 7 (Lmo7) is a novel activator of apical constriction in the Xenopus superficial ectoderm, which coordinates actomyosin contractility in a group of cells during epithelial morphogenesis. Like other apical constriction regulators, Lmo7 requires the activation of the Rho-Rock-Myosin II pathway to induce apical constriction. However, instead of increasing the phosphorylation of myosin light chain (MLC), Lmo7 binds muscle myosin II heavy chain A (NMIIA) and increases its association with actomyosin bundles at adherens junctions (AJs). Lmo7 overexpression modulates the subcellular distribution of Wtip, a tension marker at AJs, suggesting that Lmo7 generates mechanical forces at AJs. We propose that Lmo7 increases actomyosin contractility at AJs by promoting the formation of actomyosin bundles.

A 3D culture model study monitoring differentiation of dental epithelial cells into ameloblast-like cells

RSC Advances ◽  
2016 ◽  
Vol 6 (67) ◽  
pp. 62109-62118 ◽  
Author(s):  
Mayu Tadaki ◽  
Takahisa Anada ◽  
Yukari Shiwaku ◽  
Takashi Nakamura ◽  
Masanori Nakamura ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Three Dimensional ◽  
3D Culture ◽  
Epithelial Cell Line ◽  
Rat Incisor ◽  
Model Study ◽  
Culture Model ◽  
3D Culture Model ◽  
Study Monitoring

The present study was designed to investigate whether a three dimensional (3D) culture of the rat incisor-derived dental epithelial cell line SF2 enhances its differentiation into ameloblast-like cells.

scholarly journals Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues

2021 ◽  
Author(s):  
Guillermo Martinez-Ara ◽  
Nuria Taberner ◽  
Mami Takayama ◽  
Elissavet Sandaltzopoulou ◽  
Casandra Edelweiss Villava ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Sheet ◽  
Three Dimensional ◽  
Apical Surface ◽  
Apical Constriction ◽  
Mammalian Tissues ◽  
Optic Vesicles ◽  
Soft Gels ◽  
Cellular Forces ◽  
Spatiotemporal Control

During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is one of these force-generating processes, and it is necessary to modulate epithelial curvature in fundamental morphogenetic events, such as neural tube folding. The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues currently hinders the progress of the field. Here we report the development of 'OptoShroom3', a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination of individual cells in an epithelial cell sheet reduced their apical surface while illumination of groups of cells caused deformation in the adjacent regions. By using OptoShroom3, we further manipulated 3D tissue shapes. Light-induced apical constriction provoked the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids led to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.

scholarly journals Maturation of human intestinal epithelium from pluripotency in vitro

2021 ◽  
Author(s):  
Umut Kilik ◽  
Qianhui Yu ◽  
Rene Holtackers ◽  
Makiko Seimiya ◽  
Aline Xavier da Silveira dos Santos ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelium ◽  
Three Dimensional ◽  
Intestinal Cell ◽  
Cell Populations ◽  
Epithelial Tissue ◽  
Niche Factor ◽  
Cell Transcriptome ◽  
Human Intestinal Epithelium

Methods to generate human intestinal tissue from pluripotent stem cells (PSCs) open new inroads into modeling intestine development and disease. However, current protocols require organoid transplantation into an immunocompromised mouse to achieve matured and differentiated epithelial cell states. Inspired by developmental reconstructions from primary tissues, we establish a regimen of inductive cues that enable stem cell maturation and epithelial differentiation entirely in vitro. We show that the niche factor Neuregulin1 (NRG1) promotes morphological change from proliferative epithelial cysts to matured epithelial tissue in three-dimensional cultures. Single-cell transcriptome analyses reveal differentiated epithelial cell populations, including diverse secretory and absorptive lineages. Comparison to multi-organ developmental and adult intestinal cell atlases confirm the specificity and maturation state of cell populations. Altogether, this work opens a new direction to use in vitro matured epithelium from human PSCs to study human intestinal epithelium development, disease, and evolution in controlled culture environments.

scholarly journals Characterization of an Epstein-Barr virus receptor on human epithelial cells.

1992 ◽  
Vol 176 (5) ◽  
pp. 1405-1414 ◽  
Author(s):  
M Birkenbach ◽  
X Tong ◽  
L E Bradbury ◽  
T F Tedder ◽  
E Kieff
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Viral Envelope ◽  
Epithelial Cell Line ◽  
Epithelial Tissue ◽  
Barr Virus ◽  
Human Epithelial Cells ◽  
Epstein Barr

Epstein-Barr virus (EBV) adsorption to human B lymphocytes is mediated by the viral envelope glycoprotein, gp350/220, which binds to the cell surface protein, CD21, also known as the CR2 complement receptor. Human epithelial cells also express an EBV receptor. A candidate surface molecule of 195 kD has previously been identified on an epithelial cell line and explanted epithelial tissue by reactivity with the CD21 specific monoclonal antibody (mAb), HB-5a. In experiments to further characterize the epithelial cell EBV receptor, we have found that two human epithelial cell lines, RHEK-1 and HeLa, specifically bind intact EB virions. A 145-kD protein, similar in size to B lymphocyte CD21, was specifically precipitated from surface iodinated RHEK-1 cells using the HB-5a mAb, or using purified soluble gp350/220 coupled to agarose beads. The previously identified 195-kD protein did not bind to gp350/220 or react with two other anti-CD21 mAbs. CD21 homologous RNA, similar in size to the B lymphocyte CD21 mRNA, was detected in both RHEK-1 and HeLa cells. The nucleotide sequence of the epithelial cell cDNA was identical to B lymphocyte CD21. The longest clone differs from previously reported CD21 cDNAs in having additional 5' untranslated sequence. Polymerase chain reaction amplification of RHEK-1- or B lymphoblastoid-derived cDNA verified that most CD21 transcripts are initiated at least 30-50 nucleotides upstream of the previously reported mRNA cap site. These experiments demonstrate that human epithelial cells can express CD21, and that CD21 is likely to mediate EBV adsorption to epithelial cells.

scholarly journals Selective anchoring in the specific plasma membrane domain: a role in epithelial cell polarity.

1988 ◽  
Vol 107 (6) ◽  
pp. 2363-2376 ◽  
Author(s):  
P J Salas ◽  
D E Vega-Salas ◽  
J Hochman ◽  
E Rodriguez-Boulan ◽  
M Edidin
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cell ◽  
Fluorescence Recovery ◽  
Apical Surface ◽  
Collagen Gels ◽  
Surface Polarity ◽  
Basal Surface ◽  
Apical Domain ◽  
Cell Biol ◽  
In Cells

We have studied the role of restrictions to lateral mobility in the segregation of proteins to apical and basolateral domains of MDCK epithelial cells. Radioimmunoassay and semiquantitative video analysis of immunofluorescence on frozen sections showed that one apical and three basolateral glycoproteins, defined by monoclonal antibodies and binding of beta-2-microglobulin, were incompletely extracted with 0.5% Triton X-100 in a buffer that preserves the cortical cytoskeleton (Fey, E. G., K. M. Wan, and S. Penman. 1984. J. Cell Biol. 98:1973-1984; Nelson, W. T. and P. J. Veshnock. 1986. J. Cell Biol. 103:1751-1766). The marker proteins were preferentially extracted from the "incorrect" domain (i.e., the apical domain for a basolateral marker), indicating that the cytoskeletal anchoring was most effective on the "correct" domain. The two basolateral markers were unpolarized and almost completely extractable in cells prevented from establishing cell-cell contacts by incubation in low Ca++ medium, while an apical marker was only extracted from the basal surface under the same conditions. Procedures were developed to apply fluorescent probes to either the apical or the basolateral surface of live cells grown on native collagen gels. Fluorescence recovery after photobleaching of predominantly basolateral antigens showed a large percent of cells (28-52%) with no recoverable fluorescence on the basal domain but normal fluorescence recovery on the apical surface of most cells (92-100%). Diffusion coefficients in cells with normal fluorescence recovery were in the order of 1.1 x 10(-9) cm2/s in the apical domain and 0.6-0.9 x 10(-9) cm2/s in the basal surface, but the difference was not significant. The data from both techniques indicate (a) the existence of mobile and immobile protein fractions in both plasma membrane domains, and (b) that linkage to a domain specific submembrane cytoskeleton plays an important role in the maintenance of epithelial cell surface polarity.

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