Document Detail

Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos.
MedLine Citation:
PMID:  15618288     Owner:  NLM     Status:  MEDLINE    
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.
Antony W Wood; Peter J Schlueter; Cunming Duan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2004-12-23
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  19     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-23     Completed Date:  2005-08-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1024-34     Citation Subset:  IM    
Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University Avenue, Ann Arbor, Michigan 48109, USA.
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MeSH Terms
Cardiovascular Abnormalities / genetics
Cardiovascular System / embryology*
Embryo, Nonmammalian / abnormalities,  metabolism
Embryonic Development
Gene Expression / drug effects
Gene Targeting
Hematopoiesis / genetics,  physiology
Insulin-Like Growth Factor Binding Protein 2 / genetics,  physiology*
Insulin-Like Growth Factor I / genetics
Oligodeoxyribonucleotides, Antisense / genetics,  pharmacology
RNA, Messenger / analysis,  metabolism
Zebrafish / embryology*,  genetics
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Protein 2; 0/Oligodeoxyribonucleotides, Antisense; 0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I

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