Critical roles of CD146 in zebrafish vascular development. Dev Dyn 2005 Jan;232(1):232-44
Date
12/08/2004Pubmed ID
15580611DOI
10.1002/dvdy.20220Scopus ID
2-s2.0-11244290381 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
In this report, we use zebrafish as a model system to understand the importance of CD146 in vascular development. Endothelial-specific expression of CD146 was verified by whole-mount in situ hybridization. Suppression of CD146 protein expression by antisense morpholino oligonucleotides (MO) resulted in poorly developed intersomitic vessels (ISVs). In CD146 morphants, we observed a lack of blood flow through the ISV region, despite that fluorescence microangiography showed that the ISVs were present. This finding suggests that the lumens of the developing ISVs may be too narrow for proper circulation. Additionally, remodeling of the caudal vein plexus into functional vascular tubes appeared to be affected. Suppression of CD146 protein expression resulted in a circulation shunt that caused the circulation to by-pass part of the caudal artery/vein system. The same vascular defects were recapitulated by using a second morpholino oligonucleotide. This morphant expressed a truncated CD146 protein with amino acids V32 to T57 at the N terminus deleted in an in-frame manner. This region, therefore, is likely to contain elements critical for CD146 function. This study provides the first in vivo functional assessment of CD146 in embryonic development by showing that knockdown of CD146 protein expression severely hinders vascular development in zebrafish.
Author List
Chan B, Sinha S, Cho D, Ramchandran R, Sukhatme VPAuthor
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAngiography
Animals
Antigens, CD
Base Sequence
Blood Vessels
CD146 Antigen
Cloning, Molecular
DNA, Complementary
Endothelium, Vascular
Gene Expression Regulation, Developmental
In Situ Hybridization
Microscopy, Fluorescence
Molecular Sequence Data
Neural Cell Adhesion Molecules
Oligonucleotides
Protein Structure, Tertiary
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Time Factors
Zebrafish