AI Article Synopsis
- Angiogenesis is regulated by the Rac1 GTPase through the ELMO1/DOCK180 complex, which acts as a guanine nucleotide exchange factor for Rac1 during cell migration.
- In zebrafish studies, silencing elmo1 significantly disrupted vascular development, affecting various vessels and the thoracic duct.
- Netrin-1 and its receptor Unc5B were found to activate the ELMO1/DOCK180 complex, leading to Rac1 activation and proper vessel formation.
Article Abstract
Rationale: 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.
Methods And 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.
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| http://dx.doi.org/10.1161/CIRCRESAHA.109.213983 | DOI Listing |
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