中科大女学子Cell文章解析视网膜血管生成

【字体: 时间:2009年10月20日 来源:生物通

编辑推荐:

  来自基因技术公司肿瘤生物与血管新生研究部,Lexicon Pharmaceuticals公司的研究人员发现了Tspan12在视网膜血管生成过程中的重要作用。这一研究成果公布在Cell杂志上。

  

生物通报道:来自基因技术公司肿瘤生物与血管新生研究部,Lexicon Pharmaceuticals公司的研究人员发现了Tspan12在视网膜血管生成过程中的重要作用。这一研究成果公布在Cell杂志上。

文章的通讯作者是来自基因技术公司肿瘤生物与血管新生研究部资深科学家叶蔚蓝博士,其早年毕业于中国科学技术大学,后出国深造,1995年获得匹兹堡大学博士学位,现定居于美国旧金山,主要研究方向是研究肿瘤血管生成的原理。

Wnt受体Frizzled-4 (FZD4),共受体LRP5,或者配基Norrin的编码基因发生突变会扰乱视网膜血管的发育,引起眼科疾病(ophthalmic diseases),其中Norrin虽然与Wnts没有结构上的相关性,但是Norrin能与FZD4结合,从而激活Wnt途径。

在这篇文章中,研究人员发现了一种重要的视网膜血管蛋白:四旋蛋白Tspan12,这种蛋白在视网膜血管中表达,在FZD,LRP5,和Norrin突变小鼠中,可以发现Tspan12拟表型缺失。而且Tspan12也与LRP5,和Norrin存在遗传相关性。

进一步研究发现,Tspan12的过量表达能通过作用于Norrin受体复合物,极大增加Norrin/β-catenin的表达,而不是如之前发现的,促进Wnt/β-catenin的表达,并且Tspan12 siRNA能抑制的是Norrin的转录应答,而不是Wnt3A。

这些研究成果说明TAPAN12的重要作用,与Norrin多聚物互作,促进FZD4多聚物的形成,以及提升相关信号途径的生理水平。

(生物通:张迪)

 

附:
Weilan Ye(叶蔚蓝简介)
教育背景:

University of Pittsburgh, Molecular, Cellular, Developmental Biology Program, Department of Biological Sciences, Ph.D. 1995
University of Science and Technology of China (USTC), Biophysics, B.S. 1988

研究简介:
"I came to Genentech as a postdoc in October 1995 to work on neural development and neural degenerative diseases. I enjoyed the dynamic and stimulating scientific environment so much that I decided to stay as a scientist, beginning in November 1999, and started a small research program focusing on vascular development."

Current Projects
"We are interested in understanding how vascular endothelial cells are orchestrated to form a functional tubular network after the initial angiogenic induction. A better knowledge of this complex process may lead to the development of new treatment strategies for diseases associated with abnormal vascular growth.

Towards this aim, my group carried out a molecular screen based on expression patterns, and we identified a significant number of novel factors that are abundantly expressed in the developing vasculatures. We are now carrying out functional analysis of these factors using several in vivo and in vitro systems, including zebrafish knockdown, mouse knockout, organ culture, and xenograft tumor models."

Collaborations
"Over the years, as a postdoc and a scientist, I have interacted with numerous highly motivated and talented people from many departments. The strong collaborative spirit at Genentech is what makes this place productive and enjoyable. I am learning new things on a daily basis simply by being close to many excellent colleagues."

Inspiration/Vision
"Many biotech and pharmaceutical companies run their business like machines. Genentech is an exception, where scientific freedom is blended well with good business sense. Time and again, Genentech is proven to be the industry leader. This is a place where creative minds have a good chance to transform medicine."

部分发表文章:
Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W
TSPAN12 Regulates Retinal Vascular Development by Promoting Norrin- but Not Wnt-Induced FZD4/β-Catenin Signaling
Cell, 139 (2): 299-311, 2009

Evangelista M, Lim TY, Lee J, Parker L, Ashique A, Peterson AS, Ye W, Davis DP, de Sauvage FJ.
Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal transduction
Science Signaling 1(39):ra7 (2008)

Schmidt M, Paes K, De Maziere A, Smyczek T, Yang S, Gray A, French D, Kasman I, Klumperman J, Rice DS, Ye W.
EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution.
Development, 134(16): 2913-23. (2007)

Parker LH, Schmidt M, Jin SW, Gray AM, Beis D, Pham T, Frantz G, Palmieri S,
Hillan K, Stainier DY, De Sauvage FJ, Ye W.
The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation.
Nature, vol. 428 (6984): 754-8. (2004)

Craven SE, Lim KC, Ye W, Engel JD, de Sauvage FJ, Rosenthal A.
Gata2 specifies serotonergic neurons downstream of sonic hedgehog.
Development, vol. 131 (5): 1165-73. (2004)

Ye W*, Bouchard M*, Stone D, Liu X, Vella F, Lee J, Nakamura H, Ang SL, Busslinger M, Rosenthal A. (*Equal first authors)
Distinct regulators control the expression of the mid-hindbrain organizer signal FGF.
Nature Neurosci, Vol. 4(12): 1175-81. ( 2001)

Hynes M, Ye W, Wang K, Stone D, Murone M, Sauvage FJ, Rosenthal A.
The seven-transmembrane receptor smoothened cell-autonomously induces multiple ventral cell types.
Nature Neurosci, vol 3(1): p41-6. (2000)

Ye W, Shimamura K, Rubenstein J.L.R., Hynes M.A., Rosenthal. A. 
FGF and Shh Signals Control Dopaminergic and Serotonergic Cell Fate in the Anterior Neural Plate.
Cell, Vol 93(5): p755-766. (1998).

(A complete publication list can be found here: http://www.gene.com/gene/research/postdoctoral/mentors/cellbio/ye/papers.html)

原文检索:
TSPAN12 Regulates Retinal Vascular Development by Promoting Norrin- but Not Wnt-Induced FZD4/β-Catenin Signaling

Mutations in the genes encoding the Wnt receptor Frizzled-4 (FZD4), coreceptor LRP5, or the ligand Norrin disrupt retinal vascular development and cause ophthalmic diseases. Although Norrin is structurally unrelated to Wnts, it binds FZD4 and activates the canonical Wnt pathway. Here we show that the tetraspanin Tspan12 is expressed in the retinal vasculature, and loss of Tspan12 phenocopies defects seen in Fzd4, Lrp5, and Norrin mutant mice. In addition, Tspan12 genetically interacts with Norrin or Lrp5. Overexpressed TSPAN12 associates with the Norrin-receptor complex and significantly increases Norrin/β-catenin but not Wnt/β-catenin signaling, whereas Tspan12 siRNA abolishes transcriptional responses to Norrin but not Wnt3A in retinal endothelial cells. Signaling defects caused by Norrin or FZD4 mutations that are predicted to impair receptor multimerization are rescued by overexpression of TSPAN12. Our data indicate that Norrin multimers and TSPAN12 cooperatively promote multimerization of FZD4 and its associated proteins to elicit physiological levels of signaling.

 

 

相关新闻
生物通微信公众号
微信
新浪微博
  • 搜索
  • 国际
  • 国内
  • 人物
  • 产业
  • 热点
  • 科普

热搜:肿瘤|血管|Tspan12|

  • 急聘职位
  • 高薪职位

知名企业招聘

热点排行

    今日动态 | 人才市场 | 新技术专栏 | 中国科学人 | 云展台 | BioHot | 云讲堂直播 | 会展中心 | 特价专栏 | 技术快讯 | 免费试用

    版权所有 生物通

    Copyright© eBiotrade.com, All Rights Reserved

    联系信箱:

    粤ICP备09063491号