Cdc42 has important roles in postnatal angiogenesis and vasculature formation

Yuko Yoshida; Atsushi Yamada; Yoshihiro Akimoto; Kyoko Abe; Sachie Matsubara; Junri Hayakawa; Junichi Tanaka; Mitsuhiro Kinoshita; Tadashi Kato; Hiroaki Ogata; Akiko Sakashita; Kenji Mishima; Yoshiaki Kubota; Hayato Kawakami; Ryutaro Kamijo; Takehiko Iijima

doi:10.1016/j.ydbio.2021.05.002

Cdc42 has important roles in postnatal angiogenesis and vasculature formation

Dev Biol. 2021 Sep:477:64-69. doi: 10.1016/j.ydbio.2021.05.002. Epub 2021 May 18.

Authors

Yuko Yoshida¹, Atsushi Yamada², Yoshihiro Akimoto³, Kyoko Abe⁴, Sachie Matsubara⁵, Junri Hayakawa⁵, Junichi Tanaka⁶, Mitsuhiro Kinoshita⁷, Tadashi Kato⁸, Hiroaki Ogata⁸, Akiko Sakashita⁸, Kenji Mishima⁶, Yoshiaki Kubota⁹, Hayato Kawakami³, Ryutaro Kamijo⁷, Takehiko Iijima⁴

Affiliations

¹ Department of Perioperative Medicine, Division of Anesthesiology, School of Dentistry, Showa University, Tokyo, Japan; Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
² Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan. Electronic address: yamadaa@dent.showa-u.ac.jp.
³ Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan.
⁴ Department of Perioperative Medicine, Division of Anesthesiology, School of Dentistry, Showa University, Tokyo, Japan.
⁵ Laboratory for Electron Microscopy, Kyorin University School of Medicine, Tokyo, Japan.
⁶ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan.
⁷ Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
⁸ Department of Internal Medicine, Showa University Yokohama Northern Hospital, Yokohama, Japan.
⁹ Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.

PMID: 34019880
DOI: 10.1016/j.ydbio.2021.05.002

Abstract

Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 ^fl/fl; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Necropsy findings confirmed that these mice had various pathological aberrances in the vessels of most organs, such as blood flow congestion and blood cell invasion. Electron microscopic observations also revealed that capillary endothelial cells were detached from the basement membrane as well as phagocytosis of dead endothelial cells induced by macrophages. Moreover, vascular sprouting from aortic rings induced by VEGF-A was diminished in samples from the Cdc42 cKO mice because of an endothelial cell proliferation defect. These results suggest that Cdc42 in vascular endothelial cells has important roles in blood vessel formation after birth.

Keywords: Angiogenesis; Cdc42; Congestion; Rho GTPase; VE-Cadherin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Vessels / growth & development*
Endothelial Cells / physiology*
Mice
Mice, Knockout
Neovascularization, Physiologic / physiology*
cdc42 GTP-Binding Protein / physiology*

Substances

Cdc42 protein, mouse
cdc42 GTP-Binding Protein