Distinct roles of cadherin-6 and E-cadherin in tubulogenesis and lumen formation

Jia, Liwei; Liu, Fengming; Hansen, Steen Ingemann; Beest, Martin B.A. ter; Zegers, Mirjam M.

doi:10.1091/mbc.e11-01-0038

Cited by 40 publications

(42 citation statements)

References 63 publications

(101 reference statements)

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“…12,29,30 Although CDH1 and CLDN4 are components of the apical junctional complex, RAB25 appears to be important for cargo shuttling to the apical domain. Therefore, we decided to re-express each of these genes in Grhl2-KD cells to assay for their sufficiency to replace GRHL2 function.…”

Section: Grhl2 Is Required For Lumen Expansion and Epithelial Barriermentioning

confidence: 99%

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Aue

Hinze

Walentin

et al. 2015

Journal of the American Society of Nephrology

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Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia. The renal collecting duct's vital electrolyte and waterregulatory functions are carried out by highly specialized cell populations. 1 The collecting duct itself is composed of a tight epithelium, which separates the urinary compartment from a hypertonic interstitium and maintains a barrier to concentration gradients. The collecting duct derives from the ureteric bud, which emanates from the nephric duct and then undergoes branching morphogenesis in response to signals from the adjacent metanephric mesenchyme. 2 Many of the genes that are critical for aspects of nephric duct development continue to be expressed in the ureteric bud and collecting duct, serving roles in development, differentiation, and maintenance of these cells (e.g., Pax2/8, Gata3, Emx2, and Hnf1b). 3 Little is known about the molecular pathways governing the specific epithelial properties of these cells, although it is clear that these epithelia share several cell biologic properties such as a uniform tubular appearance characterized by a cuboidal epithelium surrounding a fluid-filled lumen and a molecular composition of the apical junctional complex that includes

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Section: Grhl2 Is Required For Lumen Expansion and Epithelial Barriermentioning

confidence: 99%

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Aue

Hinze

Walentin

et al. 2015

Journal of the American Society of Nephrology

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“…For instance, impaired interaction of epithelial cells with their basement membrane (O'Brien et al 2001;Myllymaki et al 2011;Daley et al 2012), or mutations in cellcell adhesion receptors (Stephenson et al 2010;Jia et al 2011) can give rise to epithelial structures in which the cells are aberrantly polarized (some of them contain an apical surface) and do not give rise to a central lumen. Thus, the polarity of each cell must properly orientate to align with the higher-order tissue architecture to generate the specific geometry needed for tissue function.…”

Section: From Individual Cell Polarity To Generation Of Epithelial Timentioning

confidence: 99%

“…First, cells send out large extensions from the basolateral surface, while retaining the apical domain (Pollack et al 1998). Extension formation requires the down-regulation of cadherin-6 and Pak1 ( p21-activated kinase 1), activation of PI3K, and up-regulation of TNS4 (tensin 4), whereas the small GTPase Rho and its effector ROCK control the length and number of extensions Kong et al 2009;Hunter and Zegers 2010;Jia et al 2011;Kwon et al 2011). Next, chains of 1-3 cells protrude and migrate out of the cyst wall (Pollack et al 1998).…”

Section: Dynamic Rearrangements Of Polarity Drive Epithelial Morphogementioning

confidence: 99%

Polarity in Mammalian Epithelial Morphogenesis

Roignot

Peng

Mostov

2013

Cold Spring Harbor Perspectives in Biology

137

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SUMMARYCell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture models has brought new insights into the mechanisms underlying the establishment and maintenance of higher-order epithelial tissue architecture, and in the dynamic remodeling of cell polarity that often occurs during development of epithelial organs. Here we discuss some important aspects of mammalian epithelial morphogenesis, from the establishment of cell polarity to epithelial tissue generation.

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“…For example, leader cell polarity in myoblasts depends on cdc42 activation mediated by recruitment of bPIX by P-cadherin, but not E-or R-cadherin (Plutoni et al 2016). Likewise, recruitment of bPIX by cadherin-6, but not E-cadherin, and associated inhibition of PI3K, likely underlies the cadherin-dependent inhibition of collective migration in a 3D epithelial model (Yu et al 2003;Jia et al 2011). Cadherin family member-specific roles in collective migration may be explained by differential sensitivity to mechanical signals.…”

Section: Specificity Of Cadherin Family Proteinsmentioning

confidence: 99%

Making Heads or Tails of It: Cell–Cell Adhesion in Cellular and Supracellular Polarity in Collective Migration

Venhuizen

Zegers

2017

Cold Spring Harb Perspect Biol

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Collective cell migration is paramount to morphogenesis and contributes to the pathogenesis of cancer. To migrate directionally and reach their site of destination, migrating cells must distinguish a front and a rear. In addition to polarizing individually, cell -cell interactions in collectively migrating cells give rise to a higher order of polarity, which allows them to move as a supracellular unit. Rather than just conferring adhesion, emerging evidence indicates that cadherin-based adherens junctions intrinsically polarize the cluster and relay mechanical signals to establish both intracellular and supracellular polarity. In this review, we discuss the various functions of adherens junctions in polarity of migrating cohorts.

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Distinct roles of cadherin-6 and E-cadherin in tubulogenesis and lumen formation

Abstract: Epithelial cadherins are shown to have distinct functions. Using a three-dimensional culture system of epithelial kidney cells, it is shown that cadherin-6 acts as an inhibitor of tubulogenesis, whereas E-cadherin controls lumen formation.

Cited by 40 publications

References 63 publications

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Polarity in Mammalian Epithelial Morphogenesis

Making Heads or Tails of It: Cell–Cell Adhesion in Cellular and Supracellular Polarity in Collective Migration

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