Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos.
IGF binding protein-2 (IGFBP-2) is an evolutionarily conserved protein that binds IGFs and modulates their biological activities. Although 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 knock-down 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 reduced blood cell number, 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.
Wood
Antony W
AW
Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University Avenue, Ann Arbor, Michigan 48109, USA.
Schlueter
Peter J
PJ
Duan
Cunming
C
D000818:Animals; D018376:Cardiovascular Abnormalities / Q000235:genetics; D002319:Cardiovascular System / Q000196:embryology*; D015536:Down-Regulation; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism; D047108:Embryonic Development; D015870:Gene Expression / Q000187:drug effects; D018390:Gene Targeting; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
D018971:Insulin-Like Growth Factor Binding Protein 2; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I