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血小板衍生生长因子受体β对于斑马鱼体节间血管形成至关重要。

Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation.

机构信息

Department of Surgery, Keck School of Medicine, University of Southern California and The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California, United States of America.

出版信息

PLoS One. 2010 Jun 25;5(6):e11324. doi: 10.1371/journal.pone.0011324.

Abstract

BACKGROUND

Platelet-derived growth factor receptor beta (PDGFRbeta) is a tyrosine kinase receptor known to affect vascular development. The zebrafish is an excellent model to study specific regulators of vascular development, yet the role of PDGF signaling has not been determined in early zebrafish embryos. Furthermore, vascular mural cells, in which PDGFRbeta functions cell autonomously in other systems, have not been identified in zebrafish embryos younger than 72 hours post fertilization.

METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the role of PDGFRbeta in zebrafish vascular development, we cloned the highly conserved zebrafish homolog of PDGFRbeta. We found that pdgfrbeta is expressed in the hypochord, a developmental structure that is immediately dorsal to the dorsal aorta and potentially regulates blood vessel development in the zebrafish. Using a PDGFR tyrosine kinase inhibitor, a morpholino oligonucleotide specific to PDGFRbeta, and a dominant negative PDGFRbeta transgenic line, we found that PDGFRbeta is necessary for angiogenesis of the intersegmental vessels.

SIGNIFICANCE/CONCLUSION: Our data provide the first evidence that PDGFRbeta signaling is required for zebrafish angiogenesis. We propose a novel mechanism for zebrafish PDGFRbeta signaling that regulates vascular angiogenesis in the absence of mural cells.

摘要

背景

血小板衍生生长因子受体 β (PDGFRβ) 是一种酪氨酸激酶受体,已知其会影响血管发育。斑马鱼是研究血管发育特定调节剂的极佳模型,但 PDGF 信号通路在早期斑马鱼胚胎中的作用尚未确定。此外,在受精后 72 小时以内的斑马鱼胚胎中,尚未鉴定到 PDGFRβ 在其他系统中具有自主作用的血管壁细胞。

方法/主要发现:为了研究 PDGFRβ 在斑马鱼血管发育中的作用,我们克隆了高度保守的 PDGFRβ 斑马鱼同源物。我们发现 pdgfrβ 在脊索中表达,脊索是位于背主动脉背面的发育结构,可能调节斑马鱼血管的发育。使用 PDGFR 酪氨酸激酶抑制剂、针对 PDGFRβ 的特定的 PDGFR 封闭性 morpholino 寡核苷酸和显性负 PDGFRβ 转基因系,我们发现 PDGFRβ 对于节间血管的血管生成是必需的。

意义/结论:我们的数据首次提供了 PDGFRβ 信号通路对于斑马鱼血管生成是必需的证据。我们提出了一种斑马鱼 PDGFRβ 信号通路的新机制,该机制在缺乏血管壁细胞的情况下调节血管血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/221d/2892519/38a8f2436b0e/pone.0011324.g001.jpg

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