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First published online 1 March 2006
doi: 10.1242/dev.02294

Development 133, 1389-1398 (2006)
Published by The Company of Biologists 2006
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PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains

Tomonori Hirose1,2,3, Mika Karasawa3, Yoshinobu Sugitani3, Masayoshi Fujisawa3, Kazunori Akimoto1, Shigeo Ohno1,* and Tetsuo Noda3,4,5

1 Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama 236-0004, Japan.
2 Kihara Memorial Yokohama Foundation for the Advancement of Life Sciences, Yokohama 244-0813, Japan.
3 Department of Cell Biology, JFCR-Cancer Institute, Tokyo 135-8550, Japan.
4 Center for Translational and Advanced Animal Research (CTAAR), Tohoku University School of Medicine, Sendai 980-8575, Japan.
5 CREST, Japan Science and Technology Corporation (JST), Saitama 332-0012, Japan.

* Author for correspondence (e-mail: ohnos{at}med.yokohama-cu.ac.jp)

Accepted 19 January 2006

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, PAR6ß and ezrin to the apical cortical domains are disturbed. By contrast, ZO1 and {alpha}4/ß1 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.

Key words: PAR3 (PARD3), Gene targeting, Epithelial cell polarity, Epithelial cyst, Heart development, Epicardium, Mouse


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