PUBLICATION
Functional analysis of zebrafish Microfibril-Associated Glycoprotein-1 (MAGP-1) in vivo reveals roles for microfibrils in both vascular development and function
- Authors
- Chen, E., Larson, J.D., and Ekker, S.C.
- ID
- ZDB-PUB-060216-3
- 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
Citation
Chen, E., Larson, J.D., and Ekker, S.C. (2006) Functional analysis of zebrafish Microfibril-Associated Glycoprotein-1 (MAGP-1) in vivo reveals roles for microfibrils in both vascular development and function. Blood. 107(11):4364-4374.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping