title: Planar cell polarity controls pancreatic beta cell differentiation and glucose homeostasis.
abstract: 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.
authors.affiliation: Swiss Institute for Experimental Cancer Research, Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Cortijo
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gouzi
authors.forename: Fadel
authors.initials: F
authors.lastname: Tissir
authors.forename: Anne
authors.initials: A
authors.lastname: Grapin-Botton
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015820:Cadherins; C498478:Celsr2 protein, mouse; C444454:Celsr3 protein, mouse; D011956:Receptors, Cell Surface; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose