Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development.

Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development.
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DOI:
10.1016/j.ydbio.2021.06.010
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发表时间:
2021-11
影响因子:
2.7
通讯作者:
Lawson ND
Lawson ND
中科院分区:
生物学3区
文献类型:
--
作者:
Ando K;Shih YH;Ebarasi L;Grosse A;Portman D;Chiba A;Mattonet K;Gerri C;Stainier DYR;Mochizuki N;Fukuhara S;Betsholtz C;Lawson ND

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血小板衍生生长因子β及其受体Pdgfrb在血管壁细胞(包括周细胞和血管平滑肌细胞)的发育中发挥重要作用。为了确定这种作用在斑马鱼中是否是保守的,我们分析了pdgfb和pdgfrb突变株。与小鼠相似,pdgfb和pdgfrb突变体斑马鱼缺乏脑周细胞,并表现出血管平滑肌覆盖的解剖学选择性损失。尽管有这些缺陷,pdgfrb突变体斑马鱼在幼虫阶段没有表现出循环缺陷。然而,从幼年期开始,我们观察到pdgfrb突变体严重的颅内出血和血管扩张,并伴有周细胞和血管平滑肌细胞的丢失。与小鼠相似,pdgfrb突变斑马鱼也显示肾小球结构缺陷,但肝星状细胞发育正常。我们还注意到冠状血管壁细胞的附着缺陷,伴随着它们发育的缺陷。总之,我们的研究支持壁细胞中Pdgfrb信号传导的保守要求。此外,这些斑马鱼突变体提供了一个重要的模型,在胚胎早期阶段的壁细胞的明确调查,而不会混淆循环缺陷的继发性影响。
Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle cells. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these zebrafish mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.
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