Fibrocystin Is Essential to Cellular Control of Adhesion and Epithelial Morphogenesis.

International Journal of Molecular Sciences
Wolfgang H ZieglerDieter Haffner

Abstract

Mutations of the Pkhd1 gene cause autosomal recessive polycystic kidney disease (ARPKD). Pkhd1 encodes fibrocystin/polyductin (FPC), a ciliary type I membrane protein of largely unknown function, suggested to affect adhesion signaling of cells. Contributions of epithelial cell adhesion and contractility to the disease process are elusive. Here, we link loss of FPC to defective epithelial morphogenesis in 3D cell culture and altered cell contact formation. We study Pkhd1-silenced Madin-Darby Canine Kidney II (MDCKII) cells using an epithelial morphogenesis assay based on micropatterned glass coverslips. The assay allows analysis of cell adhesion, polarity and lumen formation of epithelial spheroids. Pkhd1 silencing critically affects the initial phase of the morphogenesis assay, leading to a reduction of correctly polarized spheroids by two thirds. Defects are characterized by altered cell adhesion and centrosome positioning of FPC-deficient cells in their 1-/2-cell stages. When myosin II inhibitor is applied to reduce cellular tension during the critical early phase of the assay, Pkhd1 silencing no longer inhibits formation of correctly polarized epithelia. We propose that altered sensing and cell interaction of FPC-deficient e...Continue Reading

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Citations

Jul 31, 2021·Cellular and Molecular Gastroenterology and Hepatology·Murali K YandaLiudmila Cebotaru
Nov 10, 2021·Clinical Science·Anastasia V SudarikovaDaria V Ilatovskaya

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Methods Mentioned

BETA
chips
PCR
chip
transfection

Software Mentioned

FeatureJ
AxioVision
MATLAB
CircStat ” Circular Statistics Toolbox
GraphPad Prism
Image Studio
ImageJ

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