Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

Cerruti, Benedetta; Shewan, Annette M.; Yu, Wei; Combes, Alexander N.; Little, Melissa H.; Chianale, Federica; Primo, Luca; Serini, Guido; Mostov, Keith E.; Celani, Antonio; Gamba, A.

doi:10.1085/jgp.1425oia43

Cited by 9 publications

(15 citation statements)

References 23 publications

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“…6A). Second, whereas inhibition of ROCK prevented tubular lumen consolidation, depletion of ROCK did not impair lumen formation in cysts (Cerruti et al, 2013;Yu et al, 2008). Third, the number and location of lumens in cysts depend, at least in part, on oriented cell division (Jaffe et al, 2008;Schluter et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

Kim

Shewan

Ewald

et al. 2015

Journal of Cell Science

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Tubulogenesis is fundamental to the development of many epithelial organs. Although lumen formation in cysts has received considerable attention, less is known about lumenogenesis in tubes. Here, we utilized tubulogenesis induced by hepatocyte growth factor (HGF) in MDCK cells, which form tubes enclosing a single lumen. We report the mechanism that controls tubular lumenogenesis and limits each tube to a single lumen. Knockdown of p114RhoGEF (also known as ARHGEF18), a guanine nucleotide exchange factor for RhoA, did not perturb the early stages of tubulogenesis induced by HGF. However, this knockdown impaired later stages of tubulogenesis, resulting in multiple lumens in a tube. Inhibition of Rho kinase (ROCK) or myosin IIA, which are downstream of RhoA, led to formation of multiple lumens. We studied lumen formation by live-cell imaging, which revealed that inhibition of this pathway blocked cell movement, suggesting that cell movement is necessary for consolidating multiple lumens into a single lumen. Lumen formation in tubules is mechanistically quite different from lumenogenesis in cysts. Thus, we demonstrate a new pathway that regulates directed cell migration and formation of a single lumen during epithelial tube morphogenesis.

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Section: Discussionmentioning

confidence: 99%

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

Kim

Shewan

Ewald

et al. 2015

Journal of Cell Science

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“…This system has been popular in simulating self-organization resulting from cell-cell and cell-extracellular matrix (ECM) adhesion, where the function to be minimized is the total surface energy of the cell(s). This model has been employed to understand the growth of epithelial structures and proposes interesting interpretations of how single or multiple lumen form in cysts (Cerruti et al, 2013).…”

Section: Structured Grid Modelsmentioning

confidence: 99%

The physics of organoids: a biophysical approach to understanding organogenesis

Dahl-Jensen

Grapin-Botton

2017

Development

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Organoids representing a diversity of tissues have recently been created, bridging the gap between cell culture and experiments performed in vivo. Being small and amenable to continuous monitoring, they offer the opportunity to scrutinize the dynamics of organ development, including the exciting prospect of observing aspects of human embryo development live. From a physicist's perspective, their ability to self-organize -to differentiate and organize cells in space -calls for the identification of the simple rules that underlie this capacity. Organoids provide tractable conditions to investigate the effects of the growth environment, including its molecular composition and mechanical properties, along with the initial conditions such as cell number and type(s). From a theoretical standpoint, different types of in silico modeling can complement the measurements performed in organoids to understand the role of chemical diffusion, contact signaling, differential cell adhesion and mechanical controls. Here, we discuss what it means to take a biophysical approach to understanding organogenesis in vitro and how we might expect such approaches to develop in the future.

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“…This is followed by the formation of a pre-apical patch (PAP) that is demarcated by tight junctions and, through fluid accumulation and membrane repulsion, expansion to form a lumen (Bagnat et al, 2007;Bryant et al, 2010). Genesis of a single lumen requires coordination of polarized cell division Jaffe et al, 2008;Qin et al, 2010), fluid accumulation (Bagnat et al, 2007), membrane delivery (Weis et al, 2016) and a balance between the kinetics of proliferation, apoptosis and polarization (Cerruti et al, 2013;Martín-Belmonte et al, 2008). These cellular processes are highly regulated and do not occur in isolation.…”

Section: Introductionmentioning

confidence: 99%

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

Odenwald

Choi

Buckley

et al. 2016

Journal of Cell Science

103

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Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1-occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation.

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Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

Cited by 9 publications

References 23 publications

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

The physics of organoids: a biophysical approach to understanding organogenesis

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

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