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Wnt 信号通路组分在非洲爪蟾前肾发育过程中的表达。

Expression of Wnt signaling components during Xenopus pronephros development.

机构信息

Lerner Research Institute/Cleveland Clinic, Department of Cell Biology, Cleveland, Ohio, United States of America.

出版信息

PLoS One. 2011;6(10):e26533. doi: 10.1371/journal.pone.0026533. Epub 2011 Oct 19.

Abstract

BACKGROUND

The formation of the vertebrate kidney is tightly regulated and relies on multiple evolutionarily conserved inductive events. These are present in the complex metanephric kidney of higher vertebrates, but also in the more primitive pronephric kidney functional in the larval stages of amphibians and fish. Wnts have long been viewed as central in this process. Canonical β-Catenin-dependent Wnt signaling establishes kidney progenitors and non-canonical β-Catenin-independent Wnt signaling participate in the morphogenetic processes that form the highly sophisticated nephron structure. While some individual Wnt signaling components have been studied extensively in the kidney, the overall pathway has not yet been analyzed in depth.

METHODOLOGY/PRINCIPAL FINDINGS: Here we report a detailed expression analysis of all Wnt ligands, receptors and several downstream Wnt effectors during pronephros development in Xenopus laevis using in situ hybridization. Out of 19 Wnt ligands, only three, Wnt4, Wnt9a and Wnt11, are specifically expressed in the pronephros. Others such as Wnt8a are present, but in a broader domain comprising adjacent tissues in addition to the kidney. The same paradigm is observed for the Wnt receptors and its downstream signaling components. Fzd1, Fzd4, Fzd6, Fzd7, Fzd8 as well as Celsr1 and Prickle1 show distinct expression domains in the pronephric kidney, whereas the non-traditional Wnt receptors, Ror2 and Ryk, as well as the majority of the effector molecules are rather ubiquitous. In addition to this spatial regulation, the timing of expression is also tightly regulated. In particular, non-canonical Wnt signaling seems to be restricted to later stages of pronephros development.

CONCLUSION/SIGNIFICANCE: Together these data suggest a complex cross talk between canonical and non-canonical Wnt signaling is required to establish a functional pronephric kidney.

摘要

背景

脊椎动物肾脏的形成受到严格调控,并依赖于多个进化上保守的诱导事件。这些事件存在于高等脊椎动物复杂的后肾中,但也存在于两栖动物和鱼类幼虫阶段起作用的更原始的前肾中。Wnt 长期以来被认为是这个过程的核心。经典的β-连环蛋白依赖性 Wnt 信号通路建立了肾脏祖细胞,而非经典的β-连环蛋白非依赖性 Wnt 信号通路参与形成高度复杂的肾单位结构的形态发生过程。虽然个别 Wnt 信号通路成分在肾脏中得到了广泛研究,但总体通路尚未得到深入分析。

方法/主要发现:在这里,我们使用原位杂交技术报告了在非洲爪蟾(Xenopus laevis)前肾发育过程中所有 Wnt 配体、受体和几个下游 Wnt 效应物的详细表达分析。在 19 种 Wnt 配体中,只有 Wnt4、Wnt9a 和 Wnt11 在前肾中特异性表达。其他如 Wnt8a 也存在,但在一个更广泛的区域,包括肾脏相邻的组织。这种模式也适用于 Wnt 受体及其下游信号成分。Fzd1、Fzd4、Fzd6、Fzd7、Fzd8 以及 Celsr1 和 Prickle1 在肾前体中表现出独特的表达域,而非传统的 Wnt 受体 Ror2 和 Ryk 以及大多数效应分子则较为普遍。除了这种空间调控外,表达的时间也受到严格调控。特别是,非经典的 Wnt 信号似乎仅限于前肾发育的后期。

结论/意义:综上所述,这些数据表明,经典和非经典 Wnt 信号通路之间的复杂相互作用对于建立功能性前肾是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cd3/3197532/a62d6b3e198e/pone.0026533.g001.jpg

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