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线虫肠道管形成需要 vang-1 和 egl-15 信号。

Intestinal tube formation in Caenorhabditis elegans requires vang-1 and egl-15 signaling.

机构信息

Institute for Genetics, Heinrich-Heine-University Düsseldorf, D-40225 Düsseldorf, Germany.

出版信息

Dev Biol. 2010 Mar 15;339(2):268-79. doi: 10.1016/j.ydbio.2009.12.002. Epub 2009 Dec 11.


DOI:10.1016/j.ydbio.2009.12.002
PMID:20004187
Abstract

Understanding how epithelial organs form during morphogenesis is a major problem in developmental biology. In the present paper, we provide a detailed analysis of vang-1, the only homolog of the planar cell polarity protein Strabismus/Van Gogh in Caenorhabditis elegans. We demonstrate that during organogenesis of the intestine, (i) VANG-1 specifically interacts with PDZ 2 domain of DLG-1 (Discs large) and becomes phosphorylated by the kinase domain of the FGF-like receptor tyrosine kinase EGL-15; (ii) VANG-1 is predominantly restrained to the cell cortex but relocates to the apical junction; and (iii) in vang-1 embryos epithelial cells of the intestine are not correctly arranged along the anterior-posterior axis. To investigate what determines the disposition of the VANG-1 protein, either truncated protein forms were expressed in the intestine or RNAi was used to remove the functions of gene products previously shown to be involved in apical junction formation. Removal of the VANG-1 PDZ binding motif "-ESAV" and depletion of dlg-1 or let-413 gene functions interferes with the localization of VANG-1. In addition, egl-15 embryos show a premature relocation of VANG-1 to the apical junction, causing defects that resemble those observed in mutant vang-1 embryos and after intestine-specific overexpression of full-length vang-1. Finally, the localization of VANG-1 depends on DSH-2, a homolog of the planar cell polarity protein Dishevelled and depletion phenocopies vang-1 and egl-15 phenotypes in the embryonic intestine.

摘要

在形态发生过程中理解上皮器官的形成是发育生物学中的一个主要问题。在本文中,我们对 vang-1 进行了详细分析,vang-1 是秀丽隐杆线虫中平面细胞极性蛋白 Strabismus/Van Gogh 的唯一同源物。我们证明,在肠的器官发生过程中,(i)VANG-1 特异性地与 PDZ2 结构域的 DLG-1(Discs large)相互作用,并被 FGF 样受体酪氨酸激酶 EGL-15 的激酶结构域磷酸化;(ii)VANG-1 主要被限制在细胞膜皮质,但重新定位到顶端连接;(iii)在 vang-1 胚胎中,肠上皮细胞没有沿着前后轴正确排列。为了研究什么决定了 VANG-1 蛋白的分布,我们在肠中表达了截短的蛋白形式,或者使用 RNAi 去除以前被证明参与顶端连接形成的基因产物的功能。去除 VANG-1 的 PDZ 结合基序“-ESAV”和 dlg-1 或 let-413 基因功能的缺失会干扰 VANG-1 的定位。此外,egl-15 胚胎中 VANG-1 过早地重新定位到顶端连接,导致类似于突变 vang-1 胚胎和肠特异性全长 vang-1 过表达后观察到的缺陷。最后,VANG-1 的定位取决于 DSH-2,DSH-2 是平面细胞极性蛋白 Dishevelled 的同源物,其缺失表型类似于 vang-1 和 egl-15 在胚胎肠中的表型。

相似文献

[1]
Intestinal tube formation in Caenorhabditis elegans requires vang-1 and egl-15 signaling.

Dev Biol. 2009-12-11

[2]
The planar cell polarity protein VANG-1/Vangl negatively regulates Wnt/β-catenin signaling through a Dvl dependent mechanism.

PLoS Genet. 2018-12-7

[3]
VANG-1 and PRKL-1 cooperate to negatively regulate neurite formation in Caenorhabditis elegans.

PLoS Genet. 2011-9-1

[4]
The C. elegans ezrin-radixin-moesin protein ERM-1 is necessary for apical junction remodelling and tubulogenesis in the intestine.

Dev Biol. 2004-8-1

[5]
C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.

PLoS One. 2012-2-16

[6]
The apical disposition of the Caenorhabditis elegans intestinal terminal web is maintained by LET-413.

Dev Biol. 2004-4-15

[7]
FGF signaling functions in the hypodermis to regulate fluid balance in C. elegans.

Development. 2004-6

[8]
The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis.

Development. 2018-12-17

[9]
Dishevelled attenuates the repelling activity of Wnt signaling during neurite outgrowth in Caenorhabditis elegans.

Proc Natl Acad Sci U S A. 2015-10-27

[10]
Van Gogh and Frizzled act redundantly in the Drosophila sensory organ precursor cell to orient its asymmetric division.

PLoS One. 2009

引用本文的文献

[1]
Wnt-Ror-Dvl signalling and the dystrophin complex organize planar-polarized membrane compartments in C. elegans muscles.

Nat Commun. 2024-6-10

[2]
Bma-LAD-2, an Intestinal Cell Adhesion Protein, as a Potential Therapeutic Target for Lymphatic Filariasis.

mBio. 2022-6-28

[3]
Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of the DREAM Repressor Complex.

G3 (Bethesda). 2020-2-6

[4]
Linking Cell Polarity to Cortical Development and Malformations.

Front Cell Neurosci. 2019-6-4

[5]
Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation.

J Cell Biol. 2018-12-31

[6]
The planar cell polarity protein VANG-1/Vangl negatively regulates Wnt/β-catenin signaling through a Dvl dependent mechanism.

PLoS Genet. 2018-12-7

[7]
Hub connectivity, neuronal diversity, and gene expression in the Caenorhabditis elegans connectome.

PLoS Comput Biol. 2018-2-12

[8]
PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based Nerve Cord Assembly in C. elegans.

Dev Cell. 2017-4-24

[9]
Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.

PLoS Genet. 2016-4-1

[10]
A combined binary interaction and phenotypic map of C. elegans cell polarity proteins.

Nat Cell Biol. 2016-3

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