Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis

Narayanan, Vani; Schappell, Laurel E.; Mayer, Carl R.; Duke, Ashley; Armiger, Travis J.; Arsenovic, Paul T.; Mohan, Ayush; Dahl, Kris Noel; Gleghorn, Jason P.; Conway, Daniel E.

doi:10.1016/j.cub.2019.12.025

Cited by 50 publications

(74 citation statements)

References 55 publications

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“…Interestingly, this CF EMT phenotype could be partially reverted by drugs that rescue CFTR. A similar protective role for CFTR in EMT induction was also found recently by other authors, reporting that CFTR activity led to increased cellular tension across E-cadherin, thus preventing expression of mesenchymal markers and EMTa-TFs [22].…”

Section: Cftr and Epithelial-mesenchymal Transition (Emt)supporting

confidence: 85%

“…These studies illustrate how fluid secretion is an important controller of these mechanical signals and importantly, how CFTR, a master regulator of fluid secretion can impact on those processes. CFTR was indeed shown to play a major role in regulating the lumen size of epithelial MDCK cell acini by controlling apical secretion of Clions that generate water influx, thus creating an osmotic pressure within the lumen [22]. CFTR inhibition was also found to prevent the formation of tubular structures in a 3D epididymal cell culture model [78].…”

Section: What Is the Major Role Of Cftr In Development?mentioning

confidence: 94%

“…In parallel with cancer, an increasing number of emerging studies show that CFTR plays a role in fundamental cellular processes such as foetal development [4][5][6][7][8][9], epithelial differentiation/ polarization [10][11][12][13][14], regeneration [15][16][17], and epithelial-mesenchymal transition (EMT) [18][19][20][21][22] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

Amaral

Pankonien

2020

IJMS

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One of the key features associated with the substantial increase in life expectancy for individuals with CF is an elevated predisposition to cancer, firmly established by recent studies involving large cohorts. With the recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and the increased long-term survival rate of individuals with cystic fibrosis (CF), this is a novel challenge emerging at the forefront of this disease. However, the mechanisms linking dysfunctional CFTR to carcinogenesis have yet to be unravelled. Clues to this challenging open question emerge from key findings in an increasing number of studies showing that CFTR plays a role in fundamental cellular processes such as foetal development, epithelial differentiation/polarization, and regeneration, as well as in epithelial–mesenchymal transition (EMT). Here, we provide state-of-the-art descriptions on the moonlight roles of CFTR in these processes, highlighting how they can contribute to novel therapeutic strategies. However, such roles are still largely unknown, so we need rapid progress in the elucidation of the underlying mechanisms to find the answers and thus tailor the most appropriate therapeutic approaches.

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Section: Cftr and Epithelial-mesenchymal Transition (Emt)supporting

confidence: 85%

Section: What Is the Major Role Of Cftr In Development?mentioning

confidence: 94%

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What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

Amaral

Pankonien

2020

IJMS

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“…They differ hence topologically from apical lumens, that are facing apical -and intrinsically non-adherent-cell interfaces (29,30). Apical lumens are directly sealed at their surface by tight junction proteins (31), limiting paracellular water leaking into the intercellular space, while allowing for the passage of selected ions (32). Such important topological differences may explain why baso-lateral cavities, in contrast to their apical counterparts, appear systematically pressurized, as they need to grow against adhesive contacts; it may also explain why tissues with multiple apical lumens may fail to spontaneously resolve into a single cavity (33).…”

mentioning

confidence: 99%

“…Such important topological differences may explain why baso-lateral cavities, in contrast to their apical counterparts, appear systematically pressurized, as they need to grow against adhesive contacts; it may also explain why tissues with multiple apical lumens may fail to spontaneously resolve into a single cavity (33). Hydraulic and osmotic flows are more and more recog- nized as essential determinants of embryo and tissue shaping (8,32,(34)(35)(36)(37)(38). However only a few physical models describe the interplay between cell mechanics, osmotic effects and fluid flow in morphogenesis (39)(40)(41)(42) and in previous models, osmolarity is most generally considered spatially homogeneous.…”

mentioning

confidence: 99%

A hydro-osmotic coarsening theory of biological cavity formation

Verge-Serandour

Turlier

2020

Preprint

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The blastocoel is a fluid-filled cavity characterizing early embryos at blastula stage. It is commonly described as the result of cell division patterning, but in tightly compacted embryos the mechanism underlying its emergence remains unclear. Based on experimental observations, we discuss an alternative physical model by which a single cavity forms by growth and coarsening of myriad of micrometric lumens interconnected through the intercellular space. Considering explicitly ion and fluid exchanges, we find that cavity formation is primarily controlled by hydraulic fluxes, with a minor influence of osmotic heterogeneities on the dynamics. Performing extensive numerical simulations on 1-dimensional chains of lumens, we show that coarsening is self-similar with a dynamic scaling exponent reminiscent of dewetting films over a large range of ion and water permeability values. Adding active pumping of ions to account for lumen growth largely enriches the dynamics: it prevents from collective collapse and leads to the emergence of a novel coalescence-dominated regime exhibiting a distinct scaling law. Finally, we prove that a spatial bias in pumping may be sufficient to position the final cavity, delineating hence a novel mode of symmetry breaking for tissue patterning. Providing generic testable predictions our hydro-osmotic coarsening theory highlights the essential roles of hydraulic and osmotic flows in development, with expected applications in early embryogenesis and lumenogenesis.

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Lung Development in a Dish: Models to Interrogate the Cellular Niche and the Role of Mechanical Forces in Development

Chernokal,

Gonyea,

Gleghorn

2023

Advances in Experimental Medicine and Biology

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Over the past decade, emphasis has been placed on recapitulating in vitro the architecture and multicellular interactions found in organs in vivo [1, 2]. Whereas traditional reductionist approaches to in vitro models enable teasing apart the precise signaling pathways, cellular interactions, and response to biochemical and biophysical cues, model systems that incorporate higher complexity are needed to ask questions about physiology and morphogenesis at the tissue scale. Significant advancements have been made in establishing in vitro models of lung development to understand cell-fate specification, gene regulatory networks, sexual dimorphism, three-dimensional organization, and how mechanical forces interact to drive lung organogenesis [3–5]. In this chapter, we highlight recent advances in the rapid development of various lung organoids, organ-on-a-chip models, and whole lung ex vivo explant models currently used to dissect the roles of these cellular signals and mechanical cues in lung development and potential avenues for future investigation (Fig. 3.1).

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Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis

Cited by 50 publications

References 55 publications

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

A hydro-osmotic coarsening theory of biological cavity formation

Lung Development in a Dish: Models to Interrogate the Cellular Niche and the Role of Mechanical Forces in Development

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