Epithelial Shaping by Diverse Apical Extracellular Matrices Requires the Nidogen Domain Protein DEX-1 in Caenorhabditis elegans
Epithelial Shaping by Diverse Apical Extracellular Matrices Requires the Nidogen Domain Protein DEX-1 in Caenorhabditis elegans
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DOI：
10.1534/genetics.118.301752
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发表时间：
2019-01-01
期刊：
影响因子：
3.3
通讯作者：
Sundaram, Meera, V
中科院分区：
文献类型：
--
作者：
Cohen, Jennifer D.;Flatt, Kristen M.;Sundaram, Meera, V
身体的外表面和生物管的内部（如血管系统）衬有富含脂质、糖蛋白和糖胺聚糖的顶端细胞外基质 (aECM)。 aECM 是人体抵御传染源的第一道防线，可促进组织完整性和形态发生，但相对于基底膜和基质 ECM 的描述很少。虽然一些 aECM 成分，例如透明带 (ZP) 结构域蛋白，已被鉴定，但关于 aECM 的整体组成或不同 aECM 成分共同塑造上皮组织的机制，人们知之甚少。在秀丽隐杆线虫中，外部上皮在胶原角质层分泌之前，在含 ZP 的 aECM 中发育不明确。线虫有 43 个基因，编码至少 65 种独特的 ZP 蛋白，我们发现其中一些在胚胎中包含独特的前角质层 aECM。此前，巢蛋白和 EGF 结构域蛋白 DEX-1 与 ZP 蛋白 DYF-7 协同作用，将树突锚定到秀丽隐杆线虫鼻尖上。在这里，我们鉴定了 dex-1 的一个新的、强功能丧失等位基因，即 cs201。 dex-1 突变体在 L1 幼虫时死亡，并具有多种组织变形表型，包括排泄缺陷、咽部侵入、翼状缺陷以及短而胖的体形，与编码 ZP 蛋白的基因非常相似。 DEX-1 定位于组织中含有 ZP 的 aECM，这些组织显示出 dex-1 突变体的缺陷。我们的研究表明，DEX-1 是多种不同胚胎 aECM 的组成部分，这些 aECM 形成发育中的上皮细胞，并且是多种 ZP 蛋白的潜在伴侣。
The body's external surfaces and the insides of biological tubes, like the vascular system, are lined by a lipid-, glycoprotein-, and glycosaminoglycan-rich apical extracellular matrix (aECM). aECMs are the body's first line of defense against infectious agents and promote tissue integrity and morphogenesis, but are poorly described relative to basement membranes and stromal ECMs. While some aECM components, such as zona pellucida (ZP) domain proteins, have been identified, little is known regarding the overall composition of the aECM or the mechanisms by which different aECM components work together to shape epithelial tissues. In Caenorhabditis elegans, external epithelia develop in the context of an ill-defined ZP-containing aECM that precedes secretion of the collagenous cuticle. C. elegans has 43 genes that encode at least 65 unique ZP proteins, and we show that some of these comprise distinct precuticle aECMs in the embryo. Previously, the nidogen- and EGF-domain protein DEX-1 was shown to anchor dendrites to the C. elegans nose tip in concert with the ZP protein DYF-7. Here, we identified a new, strong loss-of-function allele of dex-1, cs201. dex-1 mutants die as L1 larvae and have a variety of tissue distortion phenotypes, including excretory defects, pharyngeal ingression, alae defects, and a short and fat body shape, that strongly resemble those of genes encoding ZP proteins. DEX-1 localizes to ZP-containing aECMs in the tissues that show defects in dex-1 mutants. Our studies suggest that DEX-1 is a component of multiple distinct embryonic aECMs that shape developing epithelia, and a potential partner of multiple ZP proteins.