scholarly journals Dia1 Coordinates Differentiation and Cell Sorting in a Stratified Epithelium

2021 ◽  
Author(s):  
Robert M. Harmon ◽  
John Devany ◽  
Margaret L. Gardel

AbstractAlthough implicated in adhesion, few studies address how actin assembly factors guide cell positioning in multicellular tissue. The formin, Dia1, localizes to the proliferative basal layer of epidermis. In organotypic cultures, Dia1 depletion reduced basal cell density and resulted in stratified tissue with disorganized differentiation and proliferative markers. Since crowding induces differentiation in epidermal tissue, we hypothesized that Dia1 allows cells to reach densities amenable to differentiation prior to stratification. Consistent with this hypothesis, forced crowding of Dia1-deficient cells rescued transcriptional abnormalities. Dia1 promotes rapid growth of lateral adhesions, a behavior consistent with the ability of cells to remain monolayered when crowded. In aggregation assays, cells sorted into distinct layers based on Dia1 expression status. These results suggested that as basal cells proliferate, reintegration and packing of Dia1-positive daughter cells is favored while Dia1-negative cells tend to delaminate to a suprabasal compartment. These data demonstrate how formin expression patterns play a crucial role in constructing distinct domains within stratified epithelia.SummaryHarmon et al demonstrate that differential expression of an actin nucleator, the formin, Dia1, drives cell sorting and maintains distinct morphological domains within an epithelial tissue. This illuminates the possible utility of evolving a large formin family in orchestrating the compartmentalization and differentiation of complex tissues.

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1945
Author(s):  
Sheyla González ◽  
Maximilian Halabi ◽  
David Ju ◽  
Matthew Tsai ◽  
Sophie X. Deng

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.


2002 ◽  
Vol 13 (3) ◽  
pp. 162-165 ◽  
Author(s):  
Rodrigo de Castro Albuquerque ◽  
Ricardo Santiago Gomez ◽  
Rodrigo Aliprandi Dutra ◽  
Wallison Arthuso Vasconcellos ◽  
Renato Santiago Gomez ◽  
...  

The purpose of the present study was to evaluate the influence of short course topical application of carbamide peroxide on proliferating cell nuclear antigen (PCNA) immunohistochemical expression in the oral tongue mucosa of rats. Twelve male Wistar rats were submitted to topical application of 10% carbamide peroxide on one side of the dorsal tongue once a week for three consecutive weeks. Only distilled water was applied on the control side. The animals were killed on days 0, 10, and 20 after the last application. The tongue was fixed in buffered formalin for 24 h and embedded in paraffin. Tissue blocks (3 µm) were subjected to the biotin-streptavidin amplified system for identification of PCNA. The percentage of epithelial-positive basal cells in each side of the tongue mucosa was calculated. The results demonstrated that topical application of 10% carbamide peroxide increases PCNA immunohistochemical expression on the basal layer of the oral mucosa epithelium of rats on day 0 after treatment. In conclusion, short-course use of carbamide peroxide induces transient epithelial cell proliferation of the oral mucosa of rats.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammed Akhtar ◽  
Sameera Rashid ◽  
Mohamed Ben Gashir ◽  
Noheir Mostafa Taha ◽  
Issam Al Bozom

Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.


2020 ◽  
Vol 33 (7) ◽  
pp. 1077-1086 ◽  
Author(s):  
Yun-Jae Park ◽  
Ji-Hyuk Kim ◽  
Hack-Youn Kim ◽  
Hee-Bok Park ◽  
Juhui Choe ◽  
...  

Objective: We examined the localization and expression of H<sup>+ pumping vacuolar ATPase (V-ATPase) and cytokeratin 5 (KRT5) in the epididymis of pigs, expressed in clear and basal cells, respectively, during postnatal development.Methods: Epididymides were obtained from pigs at 1, 7, 21, 60, 120, and 180 days of age; we observed the localization and expression patterns of V-ATPase and KRT5 in the different regions of these organs, namely, the caput, corpus, and cauda. The differentiation of epididymal epithelial cells was determined by immunofluorescence labeling using cell-type-specific markers and observed using confocal microscopy.Results: At postnatal day 5 (PND5), the localization of clear cells commenced migration from the cauda toward the caput. Although at PND120, goblet-shaped clear cells were detected along the entire length of the epididymis, those labeled for V-ATPase had disappeared from the corpus to cauda and were maintained only in the caput epididymis in adult pigs. In contrast, whereas basal cells labeled for KRT5 were only present in the vas deferens at birth, they were detected in all regions of the epididymis at PND60. These cells were localized at the base of the epithelium; however, no basal cells characterized by luminally extending cell projections were observed in any of the adult epididymides examined.Conclusion: The differentiation of clear and basal cells progressively initiates in a retrograde manner from the cauda to the caput epididymis. The cell-type-specific distribution and localization of the epithelial cells play important roles in establishing a unique luminal environment for sperm maturation and storage in the pig epididymis.


2005 ◽  
Vol 170 (5) ◽  
pp. 803-812 ◽  
Author(s):  
Anne Pacquelet ◽  
Pernille Rørth

Cadherin-mediated adhesion can be regulated at many levels, as demonstrated by detailed analysis in cell lines. We have investigated the requirements for Drosophila melanogaster epithelial (DE) cadherin regulation in vivo. Investigating D. melanogaster oogenesis as a model system allowed the dissection of DE-cadherin function in several types of adhesion: cell sorting, cell positioning, epithelial integrity, and the cadherin-dependent process of border cell migration. We generated multiple fusions between DE-cadherin and α-catenin as well as point-mutated β-catenin and analyzed their ability to support these types of adhesion. We found that (1) although linking DE-cadherin to α-catenin is essential, regulation of the link is not required in any of these types of adhesion; (2) β-catenin is required only to link DE-cadherin to α-catenin; and (3) the cytoplasmic domain of DE-cadherin has an additional specific function for the invasive migration of border cells, which is conserved to other cadherins. The nature of this additional function is discussed.


2001 ◽  
Vol 204 (12) ◽  
pp. 2049-2061 ◽  
Author(s):  
Marie-Dominique Franco ◽  
Michael P. Pape ◽  
Jennifer J. Swiergiel ◽  
Gail D. Burd

SUMMARY In Xenopus laevis, the formation of the adult olfactory epithelium involves embryonic, larval and metamorphic phases. The olfactory epithelium in the principal cavity (PC) develops during embryogenesis from the olfactory placode and is thought to respond to water-borne odorants throughout larval life. During metamorphosis, the PC undergoes major transformations and is exposed to air-borne odorants. Also during metamorphosis, the middle cavity (MC) develops de novo. The olfactory epithelium in the MC has the same characteristics as that in the larval PC and is thought to respond to water-borne odorants. Using in situ hybridization, we analyzed the expression pattern of the homeobox genes X-dll3 and Pax-6 within the developing olfactory system. Early in development, X-dll3 is expressed in both the neuronal and non-neuronal ectoderm of the sense plate and in all cell layers of the olfactory placode and larval PC. Expression becomes restricted to the neurons and basal cells of the PC by mid-metamorphosis. During metamorphosis, X-dll3 is also expressed throughout the developing MC epithelium and becomes restricted to neurons and basal cells at metamorphic climax. This expression pattern suggests that X-dll3 is first involved in the patterning and genesis of all cells forming the olfactory tissue and is then involved in neurogenesis or neuronal maturation in putative water- and air-sensing epithelia. In contrast, Pax-6 expression is restricted to the olfactory placode, larval PC and metamorphic MC, suggesting that Pax-6 is specifically involved in the formation of water-sensing epithelium. The expression patterns suggest that X-dll3 and Pax-6 are both involved in establishing the olfactory placode during embryonic development, but subtle differences in cellular and temporal expression patterns suggest that these genes have distinct functions.


1974 ◽  
Vol 15 (2) ◽  
pp. 291-319
Author(s):  
T. D. ALLEN ◽  
C. S. POTTEN

Mouse dorsal interfollicular epidermis has a vertical organization consisting of approximately 1400 units/mm2. Each unit is identified by its uppermost 4 to 6 layers of roughly hexagonal flattened cornified cells or squames, which are stacked in a precise vertical column. Beneath each column of squames there are 3 differentiating cells and a group of 10 or 11 basal cells, which provide cells to replace those lost by desquamation at the top of the squame column. The whole unit is termed an epidermal proliferative unit or EPU. In the central region of the basal layer of each EPU is a single dendritic Langerhans cell, devoid of desmosomes, but held in position by the surrounding keratinocytes. The dendrites radiate outwards between the keratinocytes to the periphery of the unit. Keratinocyte migration into the spinous layer takes place from the edge of the unit. In the squame column itself, a modified cell-to-cell attachment (squamosome) runs around the edge of each cornified cell, and attaches it to the overlapping region of cells from adjacent squame columns.


Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 891-903
Author(s):  
Ishara S. Ariyapala ◽  
Jessica M. Holsopple ◽  
Ellen M. Popodi ◽  
Dalton G. Hartwick ◽  
Lily Kahsai ◽  
...  

The Drosophila adult midgut is a model epithelial tissue composed of a few major cell types with distinct regional identities. One of the limitations to its analysis is the lack of tools to manipulate gene expression based on these regional identities. To overcome this obstacle, we applied the intersectional split-GAL4 system to the adult midgut and report 653 driver combinations that label cells by region and cell type. We first identified 424 split-GAL4 drivers with midgut expression from ∼7300 drivers screened, and then evaluated the expression patterns of each of these 424 when paired with three reference drivers that report activity specifically in progenitor cells, enteroendocrine cells, or enterocytes. We also evaluated a subset of the drivers expressed in progenitor cells for expression in enteroblasts using another reference driver. We show that driver combinations can define novel cell populations by identifying a driver that marks a distinct subset of enteroendocrine cells expressing genes usually associated with progenitor cells. The regional cell type patterns associated with the entire set of driver combinations are documented in a freely available website, providing information for the design of thousands of additional driver combinations to experimentally manipulate small subsets of intestinal cells. In addition, we show that intestinal enhancers identified with the split-GAL4 system can confer equivalent expression patterns on other transgenic reporters. Altogether, the resource reported here will enable more precisely targeted gene expression for studying intestinal processes, epithelial cell functions, and diseases affecting self-renewing tissues.


1971 ◽  
Vol 3 (2) ◽  
pp. 210-211 ◽  
Author(s):  
Trevor Williams ◽  
Rolf Bjerknes

When a basal cell divides, both daughter cells remain in the basal layer of the epithelium, with one of the neighbouring cells being pushed out to make room. This fact opens the possibility that a cell with a heritable advantage over the normal cells may gradually produce a clone covering more and more of the basal layer. The advantage in question may consist in a faster rate of division than normal, or a more tenacious hold on the basement membrane; we shall limit consideration to the former situation.


Author(s):  
Nobuhisa Takase ◽  
Satoshi Suzuki ◽  
Tetsu Nakamura ◽  
Masashi Yamamoto ◽  
Shingo Kanaji ◽  
...  

Abstract Verrucous squamous cell carcinoma (VSCC) is a rare esophageal tumor histologically defined as a well-differentiated subtype. We present a rare case that was diagnosed as esophageal VSCC preoperatively. A 62-year-old Japanese male was referred to our hospital for further evaluation, presenting with anorexia and postcibal vomiting. An esophagogastroduodenoscopy (EGD) examination showed esophageal stricture with white-colored papillary nodules in the lower esophagus. We performed repeated superficial endoscopic biopsies of the lesion, but the histological findings showed nonspecific changes. With an endoscopic boring biopsy, the lesion showed an endophytic growth pattern, well-differentiated SCC with minimal cellular atypia and rare mitosis, and mature squamous epithelium with extensive keratinization. We preoperatively diagnosed the lesion as esophageal VSCC, and we performed a video-assisted thoracoscopic subtotal esophagectomy and cardiectomy with the patient in the prone position. Histological findings revealed that the invasive well-differentiated SCC extended into the esophageal adventitia and the stomach wall with a pushing border. Regional lymph node metastasis and vascular invasion were negative. The expression of Ki-67 was distributed mainly in the basal cells rather than parabasal cells. Without a conclusive diagnosis, a certain degree of diagnostic prediction is possible by understanding the clinical manifestations, macroscopic form and histology around the basal cells. It is helpful to obtain the high accuracy provided by an endoscopic biopsy including the basal layer in order to avoid the diagnostic dilemma that is often presented by esophageal VSCC.


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