The Rac1 regulator ELMO1 controls vascular morphogenesis in zebrafish.
BACKGROUND
Angiogenesis is regulated by the small GTPase Rac1. The ELMO1/DOCK180 complex forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems.


OBJECTIVE
To investigate the function of ELMO1/DOCK180 in vascular development.


RESULTS
In situ hybridization studies for elmo1 identified a vascular and neuronal expression in zebrafish. Morpholino-based expression silencing of elmo1 severely impaired the formation of the vasculature, including intersomitic vessels, the dorsal longitudinal anastomotic vessel, the parachordal vessel, and the development of the thoracic duct in tg(fli1:EGFP) embryos. Mechanistically, we identified Netrin-1 and its receptor Unc5B as upstream activators of the ELMO1/DOCK180 complex, regulating its functional interaction and leading to Rac1 activation in endothelial cells and vessel formation in zebrafish.


CONCLUSIONS
Our data have identified a novel signaling cascade regulating vasculature formation in zebrafish.
Epting
Daniel
D
Center for Biomedicine and Medical Technology Mannheim, Research Division Vascular Biology of the Medical Faculty Mannheim, Heidelberg University and the German Cancer Research Center (DKFZ-ZMBH Alliance) Heidelberg, Mannheim, Germany.
Wendik
Björn
B
Bennewitz
Katrin
K
Dietz
Christian T
CT
Driever
Wolfgang
W
Kroll
Jens
J
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D002417:Cattle; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C524050:Dock1 protein, zebrafish; C465214:ELMO1 protein, human; D029961:Zebrafish Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein