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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4364-4374. Prepublished online as a Blood First Edition Paper on February 9, 2006; DOI 10.1182/blood-2005-02-0789. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-02-0789v1 107/11/4364    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, E. Articles by Ekker, S. C. Search for Related Content PubMed PubMed Citation Articles by Chen, E. Articles by Ekker, S. C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Functional analysis of zebrafish microfibril-associated glycoprotein-1 (Magp1) in vivo reveals roles for microfibrils in vascular development and function Eleanor Chen, Jon D. Larson, and Stephen C. Ekker From the Arnold and Mabel Beckman Center for Transposon Research, Department of Genetics, Cell Biology and Development, and the Department of Preventive Sciences, University of Minnesota, Minneapolis. Mutations in fibrillin-1 (FBN1) result in Marfan syndrome, demonstrating a critical requirement for microfibrils in vessel structure and function. However, the identity and function of many microfibril-associated molecules essential for vascular development and function have yet to be characterized. In our morpholino-based screen for members of the secretome required for vascular development, we identified a key player in microfibril formation in zebrafish embryogenesis. Microfibril-associated glycoprotein-1 (MAGP1) is a conserved protein found in mammalian and zebrafish microfibrils. Expression of magp1 mRNA is detected in microfibril-producing cells. Analysis of a functional Magp1-mRFP fusion protein reveals localization along the midline and in the vasculature during embryogenesis. Underexpression and overexpression analyses demonstrate that specific Magp1 protein levels are critical for vascular development. Integrin function is compromised in magp1 morphant embryos, suggesting that reduced integrin–matrix interaction is the main mechanism for the vascular defects in magp1 morphants. We further show that Magp1 and fibrillin-1 interact in vivo. This study implicates MAGP1 as a key player in microfibril formation and integrity during development. The essential role for MAGP1 in vascular morphogenesis and function also supports a wide range of clinical applications, including therapeutic targets in vascular disease and cardiovascular tissue engineering. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Matrix rules: microfibrillar protein controls vascular development Tatiana V. Byzova Blood 2006 107: 4202-4203. [Full Text] [PDF] This article has been cited by other articles: A. W.Y. Chung, K. Au Yeung, G. G.S. Sandor, D. P. Judge, H. C. Dietz, and C. van Breemen Loss of Elastic Fiber Integrity and Reduction of Vascular Smooth Muscle Contraction Resulting From the Upregulated Activities of Matrix Metalloproteinase-2 and -9 in the Thoracic Aortic Aneurysm in Marfan Syndrome Circ. Res., August 31, 2007; 101(5): 512 - 522. [Abstract] [Full Text] [PDF] H. Zhong, X. Wu, H. Huang, Q. Fan, Z. Zhu, and S. Lin Vertebrate MAX-1 is required for vascular patterning in zebrafish PNAS, November 7, 2006; 103(45): 16800 - 16805. [Abstract] [Full Text] [PDF]

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