?E-Catenin Is a Positive Regulator of Pancreatic Islet Cell Lineage Differentiation.

ABSTRACT: The development and function of epithelia depend on the establishment and maintenance of cell-cell adhesion and intercellular junctions, which operate as mechanosensor hubs for the transduction of biochemical signals regulating cell proliferation, differentiation, survival, and regeneration. Here, we show that ?E-catenin, a key component of adherens junctions, functions as a positive regulator of pancreatic islet cell lineage differentiation by repressing the sonic hedgehog pathway (SHH). Thus, deletion of ?E-catenin in multipotent pancreatic progenitors resulted in (1) loss of adherens junctions, (2) constitutive activation of SHH, (3) decrease in islet cell lineage differentiation, and (4) accumulation of immature Sox9+ progenitors. Pharmacological blockade of SHH signaling in pancreatic organ cultures and in vivo rescued this defect, allowing ?E-catenin-null Sox9+ pancreatic progenitors to differentiate into endocrine cells. The results uncover crucial functions of ?E-catenin in pancreatic islet development and harbor significant implications for the design of ? cell replacement and regeneration therapies in diabetes.

SUBMITTER: Jimenez-Caliani AJ 

PROVIDER: S-EPMC5611824 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature