1 Developmental biology - endoderm and pancreas development Lab, The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet2 BasicStem NNF, The Danish Center for Stem Cell Research, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Developmental biology - endoderm and pancreas development Lab, The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet
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.