ZFIN ID: ZDB-PUB-060216-3
Functional analysis of zebrafish Microfibril-Associated Glycoprotein-1 (MAGP-1) in vivo reveals roles for microfibrils in both vascular development and function
Chen, E., Larson, J.D., and Ekker, S.C.
Date: 2006
Source: Blood 107(11): 4364-4374 (Journal)
Registered Authors: Ekker, Stephen C., Larson, Jon D.
Keywords: none
MeSH Terms:
  • Animals
  • Blood Vessels/growth & development*
  • Blood Vessels/physiology*
  • Contractile Proteins/analysis
  • Contractile Proteins/genetics
  • Contractile Proteins/physiology*
  • Embryo, Nonmammalian
  • Extracellular Matrix Proteins/analysis
  • Extracellular Matrix Proteins/genetics
  • Extracellular Matrix Proteins/physiology*
  • Integrins/metabolism
  • Microfibrils/chemistry
  • Microfibrils/physiology*
  • Microfilament Proteins/metabolism
  • Morphogenesis
  • RNA, Messenger/analysis
  • Zebrafish/embryology
PubMed: 16469878 Full text @ Blood
Mutations in fibrillin-1 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 (MAGP-1) is a conserved protein found in mammalian and zebrafish microfibrils. Expression of MAGP-1 mRNA is detected in microfibril-producing cells. Analysis of a functional MAGP-1-mRFP fusion protein reveals localization along the midline and in the vasculature during embryogenesis. Under- and over- expression analysis demonstrates that specific MAGP-1 protein levels are critical for vascular development. Integrin function is compromised in MAGP-1 morphant embryos, suggesting that reduced integrin/matrix interaction is the main mechanism for the vascular defects in MAGP1 morphants. We further show that MAGP-1 and Fibrillin-1 interact in vivo. This study implicates MAGP-1 as a key player in microfibril formation and integrity during development. The essential role for MAGP-1 in vascular morphogenesis and function also supports a wide range of clinical applications including therapeutic targets in vascular disease and cardiovascular tissue engineering.