title: PAPCcouples the segmentation clock to somite morphogenesis by regulating N-cadherin-dependent adhesion.
abstract: Vertebrate segmentation is characterized by the periodic formation of epithelial somites from the mesenchymal presomitic mesoderm (PSM). How the rhythmic signaling pulse delivered by the segmentation clock is translated into the periodic morphogenesis of somites remains poorly understood. Here, we focused on the role of paraxial protocadherin (PAPC/Pcdh8) in this process. We showed that in chicken and mouse embryos,PAPCexpression is tightly regulated by the clock and wavefront system in the posterior PSM. We observed that PAPC exhibits a striking complementary pattern to N-cadherin (CDH2), marking the interface of the future somite boundary in the anterior PSM. Gain and loss of function ofPAPCin chicken embryos disrupted somite segmentation by altering the CDH2-dependent epithelialization of PSM cells. Our data suggest that clathrin-mediated endocytosis is increased in PAPC-expressing cells, subsequently affecting CDH2 internalization in the anterior compartment of the future somite. This in turn generates a differential adhesion interface, allowing formation of the acellular fissure that defines the somite boundary. Thus, periodic expression of PAPC in the anterior PSM triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.|Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden 67400, France.|Department of Pathology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.|Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, USA.|Harvard Stem Cell Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Jérome
authors.initials: J
authors.lastname: Chal
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.|Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, USA.
authors.forename: Charlène
authors.initials: C
authors.lastname: Guillot
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA pourquie@genetics.med.harvard.edu.|Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden 67400, France.|Department of Pathology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.|Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, USA.|Harvard Stem Cell Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.|Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.|Howard Hughes Medical Institute, Kansas City, MO 64110, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pourquié
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019521:Body Patterning / Q000502:physiology; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D010641:Phenotype; D000072417:Protein Domains; D000091363:Protocadherins; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D002966:Clathrin; D000091363:Protocadherins; D051880:Receptors, Notch; C489083:Cdh2 protein, mouse; C497204:Pcdh8 protein, mouse
keywords: Boundary formation; Cadherin; Cell adhesion; Endocytosis; Paraxial mesoderm; Protocadherin; Somitogenesis; Tissue morphogenesis