title: PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains.
abstract: Epithelial cysts are one of the fundamental architectures for mammalian organogenesis. Although in vitro studies using cultured epithelial cells have revealed proteins required for cyst formation, the mechanisms that orchestrate the functions of these proteins in vivo remain to be clarified. We show that the targeted disruption of the mouse Par3 gene results in midgestational embryonic lethality with defective epicardial development. The epicardium is mainly derived from epicardial cysts and essential for cardiomyocyte proliferation during cardiac morphogenesis. PAR3-deficient epicardial progenitor (EPP) cells do not form cell cysts and show defects in the establishment of apical cortical domains, but not in basolateral domains. In PAR3-deficient EPP cells, the localizations of aPKC, PAR6beta and ezrin to the apical cortical domains are disturbed. By contrast, ZO1 and alpha4/beta1 integrins normally localize to cell-cell junctions and basal domains, respectively. Our observations indicate that EPP cell cyst formation requires PAR3 to interpret the polarity cues from cell-cell and cell-extracellular matrix interactions so that each EPP cell establishes apical cortical domains. These results also provide a clear example of the proper organization of epithelial tissues through the regulation of individual cell polarity.
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama 236-0004, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirose
authors.forename: Mika
authors.initials: M
authors.lastname: Karasawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sugitani
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
mesh_terms: D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D016764:Cell Polarity; D003560:Cysts / Q000378:metabolism*; D005260:Female; D019793:Fluorescein; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D018390:Gene Targeting; D006579:Heterozygote; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009924:Organ Culture Techniques; D010496:Pericardium / Q000166:cytology / Q000254:growth & development* / Q000473:pathology; D011247:Pregnancy; D018179:Receptors, Thrombin / Q000235:genetics* / Q000502:physiology*; D015183:Restriction Mapping
chemical_list: D005456:Fluorescent Dyes; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D019793:Fluorescein