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AlphaA-crystallin expression prevents gamma-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens.αA-晶体蛋白的表达可防止斑马鱼cloche突变体晶状体中γ-晶体蛋白的不溶性和白内障形成。
Development. 2006 Jul;133(13):2585-93. doi: 10.1242/dev.02424. Epub 2006 May 25.
2
Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish.斑马鱼中不同类型血管的发育需要多种Vegf受体之间独特的基因相互作用。
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6554-9. doi: 10.1073/pnas.0506886103. Epub 2006 Apr 14.
3
Mutant-specific gene programs in the zebrafish.斑马鱼中的突变体特异性基因程序。
Blood. 2005 Jul 15;106(2):521-30. doi: 10.1182/blood-2004-11-4541. Epub 2005 Apr 12.
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Inhibitors of ocular neovascularization: promises and potential problems.眼部新生血管形成抑制剂：前景与潜在问题
JAMA. 2005 Mar 23;293(12):1509-13. doi: 10.1001/jama.293.12.1509.
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Antivascular endothelial growth factor monoclonal antibody therapy: a promising paradigm in colorectal cancer.抗血管内皮生长因子单克隆抗体疗法：结直肠癌中一种有前景的模式。
Clin J Oncol Nurs. 2005 Feb;9(1):55-60. doi: 10.1188/05.CJON.55-60.
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Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice.Flk-1（血管内皮生长因子受体2）酪氨酸残基1173在小鼠血管生成中的重要作用。
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From guts to brains: using zebrafish genetics to understand the innards of organogenesis.从内脏到大脑：利用斑马鱼遗传学了解器官发生的内在机制。
Curr Top Dev Biol. 2005;65:47-82. doi: 10.1016/S0070-2153(04)65002-2.
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Loss of gata1 but not gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos.在斑马鱼胚胎中，gata1而非gata2的缺失会将红细胞生成转变为髓细胞生成。
Dev Cell. 2005 Jan;8(1):109-16. doi: 10.1016/j.devcel.2004.12.001.
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Zebrafish scl functions independently in hematopoietic and endothelial development.斑马鱼scl在造血和内皮细胞发育过程中独立发挥作用。
Dev Biol. 2005 Jan 15;277(2):522-36. doi: 10.1016/j.ydbio.2004.09.004.
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Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos.血管内皮生长因子A（VEGF-A）参与引导VEGF受体阳性细胞至早期胚胎的前部。
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VegfA基因的重复以及KDR受体酪氨酸激酶家族的直系同源基因介导斑马鱼的血管发育。

Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish.

作者信息

Bahary Nathan, Goishi Katsutoshi, Stuckenholz Carsten, Weber Gerhard, Leblanc Jocelyn, Schafer Christopher A, Berman Sarah S, Klagsbrun Michael, Zon Leonard I

机构信息

Department of Medicine, University of Pittsburgh School of Medicine, PA15260, USA.

出版信息

Blood. 2007 Nov 15;110(10):3627-36. doi: 10.1182/blood-2006-04-016378. Epub 2007 Aug 14.

DOI:10.1182/blood-2006-04-016378
PMID:17698971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2077312/
Abstract

Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (angiogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholino-disrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa(121) and VegfAa(165) isoforms, the VegfAb isoforms VegfAb(171) and VegfAb(210) are not normally secreted when expressed in mammalian tissue culture cells. The Kdrb locus encodes a 1361-amino acid transmembrane receptor with strong homology to mammalian KDR. Combined knockdown of both RTKs leads to defects in vascular development, suggesting that they cooperate in mediating the vascular effects of VegfA in zebrafish development. Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb proteins in vitro. Taken together, our data support a model in the zebrafish, in which duplicated VegfA and multiple type III RTKs mediate vascular development.

摘要

血管内皮生长因子A（VEGFA）和III型受体酪氨酸激酶受体（RTK）对于内皮细胞的分化（血管发生）以及新毛细血管的出芽（血管生成）均是必需的。我们分离出了一个重复的斑马鱼VegfA基因座，称为VegfAb，以及一个与KDR/FLK1具有同源性的重复RTK基因座（命名为Kdrb）。经吗啉代寡核苷酸破坏的VegfAb胚胎在受精后约2至3天（dpf）之前发育出正常的循环系统，之后血管生成缺陷会使血液渗入许多组织。与VegfAa(121)和VegfAa(165)亚型不同，VegfAb亚型VegfAb(171)和VegfAb(210)在哺乳动物组织培养细胞中表达时通常不会分泌。Kdrb基因座编码一个1361个氨基酸的跨膜受体，与哺乳动物KDR具有高度同源性。两种RTK的联合敲低会导致血管发育缺陷，这表明它们在介导VegfA对斑马鱼发育的血管作用中相互协作。VegfAa和VegfAb在体外均可单独结合并促进Flk1（Kdra）和Kdrb蛋白的磷酸化。综上所述，我们的数据支持斑马鱼中的一种模型，即重复的VegfA和多种III型RTK介导血管发育。