Critical roles of CD146 in zebrafish vascular development.
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.
Chan
Barden
B
Division of Nephrology, Center for Study of the Tumor Microenvironment, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA.
Sinha
Sonia
S
Cho
Dan
D
Ramchandran
Ramani
R
Sukhatme
Vikas P
VP
D000595:Amino Acid Sequence; D000792:Angiography; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology*; D051929:CD146 Antigen; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D009841:Oligonucleotides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D015027:Zebrafish
D015703:Antigens, CD; D051929:CD146 Antigen; D018076:DNA, Complementary; D019006:Neural Cell Adhesion Molecules; D009841:Oligonucleotides; D012333:RNA, Messenger