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.
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.
Authors: David Kaluza; Jens Kroll; Sabine Gesierich; Tso-Pang Yao; Reinier A Boon; Eduard Hergenreider; Marc Tjwa; Lothar Rössig; Edward Seto; Hellmut G Augustin; Andreas M Zeiher; Stefanie Dimmeler; Carmen Urbich Journal: EMBO J Date: 2011-08-16 Impact factor: 11.598
Authors: Arda Cetinkaya; Jingwei Rachel Xiong; İbrahim Vargel; Kemal Kösemehmetoğlu; Halil İbrahim Canter; Ömer Faruk Gerdan; Nicola Longo; Ahmad Alzahrani; Mireia Perez Camps; Ekim Zihni Taskiran; Simone Laupheimer; Lorenzo D Botto; Eeswari Paramalingam; Zeliha Gormez; Elif Uz; Bayram Yuksel; Şevket Ruacan; Mahmut Şamil Sağıroğlu; Tokiharu Takahashi; Bruno Reversade; Nurten Ayse Akarsu Journal: Am J Hum Genet Date: 2016-07-28 Impact factor: 11.025
Authors: F O Kok; M Shin; C-W Ni; A Gupta; A S Grosse; A van Impel; B C Kirchmaier; J Peterson-Maduro; G Kourkoulis; I Male; D F DeSantis; S Sheppard-Tindell; L Ebarasi; C Betsholtz; S Schulte-Merker; S A Wolfe; N D Lawson Journal: Dev Cell Date: 2014-12-18 Impact factor: 12.270
Authors: H Y Wu; Y H Wu; Y Wang; M Chen; X Zhang; D Wang; Y Pan; L Li; D Liu; X M Dai; M X Dai Journal: J Endocrinol Invest Date: 2012-07-24 Impact factor: 4.256