Int. J. Dev. Biol. 54: 609 - 615 (2010)

https://doi.org/10.1387/ijdb.092929ks

Vol 54, Issue 4

XRASGRP2 is essential for blood vessel formation during Xenopus development

Original Article | Published: 1 July 2009

Kan Suzuki¹, Shuji Takahashi², Yoshikazu Haramoto², Yasuko Onuma³, Kentaro Nagamine⁴, Koji Okabayashi^5,7, Kohei Hashizume⁶, Tadashi Iwanaka¹ and Makoto Asashima*^,3,5,7

¹Department of Pediatric Surgery and Oncology, Graduate School of Medicine, and ²Center for Structuring Life Science, Graduate School of Arts and Sciences, The University of Tokyo, ³Organ Development Research Laboratory, National Institute of Advanced, Industrial Sciences and Technology (AIST), ⁴Laboratory of Biochemistry, Hiroshima International University, ⁵ICORP Project (JST), Graduate School of Arts and Science, The University of Tokyo, ⁶Tokyo-West Tokushukai Hospital and ⁷Department of Life Sciences (Biology), Graduate School of Arts and Science, The University of Tokyo, Japan

Abstract

Ras guanyl nucleotide-releasing protein 2 (RASGRP2), one of the Ras guanine exchange factors, is implicated as a critical regulator of inside-out integrin activation in human lymphocytes, neutrophils and platelets. However, the activities of this protein in endothelial cells remain unclear. In the current study, we identify a physiological function in blood vessel formation for XRASGRP2, which is the Xenopus ortholog of mammalian RASGRP2. XRASGRP2 over-expression induced ectopic vascular formation, and XRASGRP2-knockdown embryos showed delayed vascular development. We also investigated the upstream signaling of XRASGRP2 in endothelium formation. XRASGRP2 expression was up-regulated in the presence of VEGF-A and down-regulated following VEGF-A depletion. XRASGRP2 knockdown abolished the ectopic induction of endothelial cells by VEGF-A in the posterior ventral blood island. These results suggest that XRASGRP2 is essential for vascular formation during Xenopus development.

Keywords

XRASGRP2, Xenopus laevis, VEGF-A, RASGRP, vasculogenesis