ZFIN ID: ZDB-PUB-041228-24
Targeted knockdown of insulin-like growth factor binding protein-2 (IGFBP-2) disrupts cardiovascular development in zebrafish embryos
Wood, A.W., Schlueter, P.J., and Duan, C.
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.
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.