Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

TY - JOUR

T1 - Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

AU - Cortijo, Cedric

AU - Gouzi, Mathieu

AU - Tissir, Fadel

AU - Grapin-Botton, Anne

N1 - Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2012/12/27

Y1 - 2012/12/27

N2 - Planar cell polarity (PCP) refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.

AB - Planar cell polarity (PCP) refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.

U2 - 10.1016/j.celrep.2012.10.016

DO - 10.1016/j.celrep.2012.10.016

M3 - Journal article

C2 - 23177622

SN - 2211-1247

VL - 2

SP - 1593

EP - 1606

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -