The International Journal of Developmental Biology

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

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 Okabayashi5,7, 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


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.


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

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