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Patj 在调节 Crumbs 复合物和上皮极性方面的组织特异性功能。

Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity.

机构信息

GReD Laboratory, Faculté de Médecine, UMR CNRS 6293, Clermont Université, INSERM U1103, place Henri-Dunant, 63000 Clermont-Ferrand, France.

出版信息

Development. 2012 Dec;139(24):4549-54. doi: 10.1242/dev.085449. Epub 2012 Nov 7.

Abstract

Patj is described as a core component of the Crumbs complex. Along with the other components, Crumbs and Stardust, Patj has been proposed as essential for epithelial polarity. However, no proper in vivo genetic analysis of Patj function has been performed in any organism. We have generated the first null mutants for Drosophila Patj. These mutants are lethal. However, Patj is not required in all epithelia where the Crumbs complex is essential. Patj is dispensable for ectoderm polarity and embryonic development, whereas more severe defects are observed in the adult follicular epithelium, including mislocalisation of the Crumbs complex from the apical domain, as well as morphogenetic defects. These defects are similar to those observed with crumbs and stardust mutants, although weaker and less frequent. Also, gain-of-function of Crumbs and Patj mutation genetically suppress each other in follicular cells. We also show that the first PDZ domain of Patj associated with the Stardust-binding domain are sufficient to fully rescue both Drosophila viability and Crumbs localisation. We propose that the only crucial function of Patj hinges on the ability of its first two domains to positively regulate the Crumbs complex, defining a new developmental level of regulation of its dynamics.

摘要

Patj 被描述为 Crumbs 复合物的核心组成部分。与其他成分(Crumbs 和 Stardust)一起,Patj 被认为对上皮极性至关重要。然而,在任何生物体中,尚未对 Patj 功能进行适当的体内遗传分析。我们已经生成了果蝇 Patj 的第一个 null 突变体。这些突变体是致命的。然而,Patj 在所有需要 Crumbs 复合物的上皮组织中并非必需。Patj 对于外胚层极性和胚胎发育不是必需的,而在成年滤泡上皮中观察到更严重的缺陷,包括 Crumbs 复合物从顶域的定位错误,以及形态发生缺陷。这些缺陷与 crumbs 和 stardust 突变体观察到的相似,尽管较弱且不常见。此外,Crumbs 和 Patj 突变的功能获得在滤泡细胞中具有遗传抑制作用。我们还表明,Patj 与 Stardust 结合域相关的第一个 PDZ 结构域足以完全挽救果蝇的活力和 Crumbs 的定位。我们提出,Patj 的唯一关键功能取决于其前两个结构域正面调节 Crumbs 复合物的能力,从而定义了其动态的新的发育调控水平。

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