PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains
PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains
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DOI：
10.1242/dev.02294
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发表时间：
2006-04-01
期刊：
影响因子：
4.6
通讯作者：
Noda, T
中科院分区：
文献类型：
--
作者：
Hirose, T;Karasawa, M;Noda, T
上皮囊肿是哺乳动物器官发生的基本结构之一。尽管体外培养上皮细胞的研究已经揭示了囊肿形成所需的蛋白质，但在体内协调这些蛋白质功能的机制仍有待阐明。我们表明，小鼠Par3基因的靶向破坏导致妊娠中期胚胎死亡和心外膜发育缺陷。心外膜主要来源于心外膜囊肿，是心脏形态发生过程中心肌细胞增殖所必需的。缺乏par3的心外膜祖细胞（EPP）不会形成细胞囊肿，并在顶端皮质结构域的建立中表现出缺陷，但在基底外侧结构域则没有。在缺乏par3的EPP细胞中，aPKC、PAR6 β和ezrin在顶端皮质结构域的定位受到干扰。相比之下，ZO1和α 4/ β 1整合素通常分别定位于细胞-细胞连接和基底结构域。我们的观察表明，EPP细胞囊肿的形成需要PAR3解释细胞间和细胞外基质相互作用的极性线索，以便每个EPP细胞建立顶端皮质结构域。这些结果也提供了上皮组织通过调节单个细胞极性的一个清晰的例子。
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, PAR6 beta and ezrin to the apical cortical domains are disturbed. By contrast, ZO1 and alpha 4/beta 1 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.