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Review
. 2022 Apr 30;23(9):4991.
doi: 10.3390/ijms23094991.

Small GTPases and Their Regulators: A Leading Road toward Blood Vessel Development in Zebrafish

Ritesh Urade  1 , Yan-Hui Chiu  1 , Chien-Chih Chiu  1   2 , Chang-Yi Wu  1   2   3   4
Affiliations
Review

Small GTPases and Their Regulators: A Leading Road toward Blood Vessel Development in Zebrafish

Ritesh Urade et al. Int J Mol Sci. .

Abstract

Members of the Ras superfamily have been found to perform several functions leading to the development of eukaryotes. These small GTPases are divided into five major subfamilies, and their regulators can "turn on" and "turn off" signals. Recent studies have shown that this superfamily of proteins has various roles in the process of vascular development, such as vasculogenesis and angiogenesis. Here, we discuss the role of these subfamilies in the development of the vascular system in zebrafish.

Keywords: GTP-binding proteins; small GTPases; vascular development and zebrafish.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Small GTPase regulation leading to healthy vessels: Cycling of GTPases in the active state and inactive state. Their activation is governed by GEFs, which remove GDP and allow excess cytoplasmic GTP to attach. The binding of active GTPase to effector proteins aggravates the cell response to give rise to blood vessels. GAP, by increasing GTPase activity, turns off the switch for GTPases. Inactive GTPase aggregates in the cytosol via GDIs. By activating effector proteins, downstream processes led to the development of healthy blood vessels (adapted and modified from Cherfils and Zeghouf 2013 [10]).
Figure 2
Figure 2
Study the function of genes in vascular development. (A) Confocal image of transgenic fish Tg(kdrl:mCherry; fli1a:nEGFP) where mCherry expression is in the endothelial cells and GFP expression is in the nucleus at 30 hpf. The image shows clear vessel structures of the dorsal aorta (da), cardinal vein (pcv), ISV, DLAV and CVP. (B,C) Knockdown of nr2f1b in transgenic fish results in vascular defects, i.e., Fewer ISVs migrated to the top of the embryo, and fewer ISV cells migrated per ISV in morphants (hollow arrowheads and fewer numbers) than in the wild-type control (arrowheads). Scale bars in panels (B) and (C) represent 50 μm. (D–K) In situ hybridization data showed that knockdown of nr2f1b reduced the expression of vascular markers. Scale bars in figures (D–K) represent 200 μm. Images (B–K) courtesy of R.-F. Li, reproduced/adapted from Li et al. (2015) [27] with permission from J. Biomed. Sci.
Figure 3
Figure 3
Schematic drawings of the proteins involved in GTPase signals and cellular function related to the cell biological process of vascular development.
See this image and copyright information in PMC

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