αE-Catenin Is a Positive Regulator of Pancreatic Islet Cell Lineage Differentiation

Antonio J. Jimenez-Caliani, Rudolf Pillich, Wendy Yang, Giuseppe R. Diaferia, Paolo Meda, Laura Crisa, Vincenzo Cirulli

Research output: Contribution to journalArticlepeer-review

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 αE-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 αE-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 αE-catenin-null Sox9+ pancreatic progenitors to differentiate into endocrine cells. The results uncover crucial functions of αE-catenin in pancreatic islet development and harbor significant implications for the design of β cell replacement and regeneration therapies in diabetes.

Original languageEnglish
Pages (from-to)1295-1306
Number of pages12
JournalCell Reports
Volume20
Issue number6
DOIs
Publication statusPublished - Aug 8 2017

Keywords

  • adherens junctions
  • cell polarity
  • islet progenitors
  • pancreas development
  • Pdx1
  • sonic hedgehog
  • Sox9
  • Α-catenin
  • Β cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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