PUBLICATION
Targeted knockdown of insulin-like growth factor binding protein-2 (IGFBP-2) disrupts cardiovascular development in zebrafish embryos
- Authors
- Wood, A.W., Schlueter, P.J., and Duan, C.
- ID
- ZDB-PUB-041228-24
- Date
- 2005
- Source
- Molecular endocrinology (Baltimore, Md.) 19(4): 1024-1034 (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- insulin-like growth factor, insulin-like growth factor binding protein-2, zebrafish, embryo, growth, development, cardiovascular
- MeSH Terms
-
- Animals
- Cardiovascular Abnormalities/genetics
- Cardiovascular System/embryology*
- Down-Regulation
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/metabolism
- Embryonic Development
- Gene Expression/drug effects
- Gene Targeting
- Hematopoiesis/genetics
- Hematopoiesis/physiology
- Insulin-Like Growth Factor Binding Protein 2/genetics
- Insulin-Like Growth Factor Binding Protein 2/physiology*
- Insulin-Like Growth Factor I/genetics
- Oligodeoxyribonucleotides, Antisense/genetics
- Oligodeoxyribonucleotides, Antisense/pharmacology
- RNA, Messenger/analysis
- RNA, Messenger/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 15618288 Full text @ Mol. Endocrinol.
Citation
Wood, A.W., Schlueter, P.J., and Duan, C. (2005) Targeted knockdown of insulin-like growth factor binding protein-2 (IGFBP-2) disrupts cardiovascular development in zebrafish embryos. Molecular endocrinology (Baltimore, Md.). 19(4):1024-1034.
Abstract
Insulin-like growth factor binding protein-2 (IGFBP-2) is an evolutionarily conserved protein that binds insulin-like growth factors (IGFs), and modulates their biological activities. While the actions of IGFBP-2 have been well studied in vitro, we have a poor understanding of its in vivo functions, particularly during early development. Using the transparent zebrafish embryo as a model, we show that IGFBP-2 mRNA is expressed in lens epithelium and cranial boundary regions during early embryonic development, and becomes localized to the liver by the completion of embryogenesis. Targeted knockdown of IGFBP-2 by antisense morpholino-modified oligonucleotides resulted in delayed development, reduced body growth, reduced IGF-I mRNA levels, and disruptions to cardiovascular development, including hypochromic anemia, reduced blood circulation, cardiac dysfunction, and brain ventricle edema. Detailed examination of vascular tissues, using a stable transgenic line of zebrafish expressing green fluorescent protein in vascular endothelial cells, revealed specific angiogenic (vessel sprouting) defects in IGFBP-2 knockdown embryos, with effects being localized in regions associated with IGFBP-2 mRNA expression. These findings suggest that IGFBP-2 is required for general embryonic development and growth, and plays a local role in regulating vascular development in a model vertebrate organism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping