The planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

Dworkin, Sebastian; Jane, Stephen M.; Darido, Charbel

doi:10.4161/org.7.3.18431

Cited by 25 publications

(26 citation statements)

References 104 publications

(134 reference statements)

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“…PCP related signaling also plays roles in cell migration, tissue re-organization and stem cell differentiation during embryonic development, and later, in regeneration and repair (Dworkin et al, 2011; Munoz-Soriano et al, 2012). Aberrant signaling has been linked to a broad range of pathophysiologies including cancer, developmental defects, and neurological disorders (Dworkin et al, 2011; Munoz-Soriano et al, 2012; Tissir & Goffinet, 2013). The deepest mechanistic insights have come from studies of PCP in Drosophila (Maung & Jenny, 2011; Singh & Mlodzik, 2012).…”

Section: Introductionmentioning

confidence: 99%

Methods for studying planar cell polarity

Olofsson

Axelrod

2014

Methods

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Section: Introductionmentioning

confidence: 99%

Methods for studying planar cell polarity

Olofsson

Axelrod

2014

Methods

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“…The Grainyhead-like (GRHL) gene family comprises GRHL1, GRHL2, and GRHL3, which function as wound healing and injury repair genes in cutaneous tissue in Drosophila and mouse (14,36). However, their functional role in injury repair in the lung is not yet fully understood.…”

mentioning

confidence: 99%

“…HPS is a rare inherited disease affecting intracellular biogenesis of lysosome-related organelles (13). Individual mutations in HPS1 or HPS2 make these mice highly susceptible to bleomycin-induced injury-induced lung fibrosis, whereas double-mutant HPS1 and HPS2 (HPS1/2) mice develop spontaneous pulmonary fibrosis (14). Recently a radiation-induced injury model, in which Foxm1 was overexpressed, showed spontaneous pneumonitis and pulmonary fibrosis with increased expression of both interleukins and epithelial-to-mesenchymal (EMT) marker transcriptional factors such as ZEB1 (4).…”

mentioning

confidence: 99%

Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

Varma

Mahavadi

Sasikumar

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity.

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“…PCP is important in a broad array of developmental and physiological processes in vertebrates, and defects in PCP signaling have been associated with many developmental anomalies and diseases [1]. Although roles for orthologs of the Drosophila PCP genes in PCP-like processes have been uncovered in vertebrates, in some cases the phenotypes are extremely mild and great effort must be made to find any sort of defect, suggesting that PCP in vertebrates may be much more complex than in flies.…”

Section: What Is Planar Cell Polarity?mentioning

confidence: 99%

Planar cell polarity of the kidney

Schnell

Carroll

2016

Experimental Cell Research

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Planar cell polarity (PCP) or tissue polarity refers to the polarization of tissues perpendicular to the apical-basal axis. Most epithelia, including the vertebrate kidney, show signs of planar polarity. In the kidney, defects in planar polarity are attributed to several disease states including multiple forms of cystic kidney disease. Indeed, planar cell polarity has been shown to be essential for several cellular processes that appear to be necessary for establishing and maintaining tubule diameter. However, uncovering the genetic mechanisms underlying PCP in the kidney has been complicated as the roles of many of the main players are not conserved in flies and vice versa. Here, we review a number of cellular and molecular processes that can affect PCP of the kidney with a particular emphasis on the mechanisms that do not appear to be conserved in flies or that are not part of canonical determinants.

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The planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

Cited by 25 publications

References 104 publications

Methods for studying planar cell polarity

Methods for studying planar cell polarity

Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

Planar cell polarity of the kidney

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