Cdc42 regulates cranial suture morphogenesis and ossification

Ryo Aizawa; Atsushi Yamada; Tatsuaki Seki; Junichi Tanaka; Ryo Nagahama; Mikiko Ikehata; Tadashi Kato; Akiko Sakashita; Hiroaki Ogata; Daichi Chikazu; Koutaro Maki; Kenji Mishima; Matsuo Yamamoto; Ryutaro Kamijo

doi:10.1016/j.bbrc.2019.02.106

Cdc42 regulates cranial suture morphogenesis and ossification

Biochem Biophys Res Commun. 2019 Apr 30;512(2):145-149. doi: 10.1016/j.bbrc.2019.02.106. Epub 2019 Mar 7.

Authors

Ryo Aizawa¹, Atsushi Yamada², Tatsuaki Seki³, Junichi Tanaka⁴, Ryo Nagahama⁵, Mikiko Ikehata⁶, Tadashi Kato⁷, Akiko Sakashita⁸, Hiroaki Ogata⁸, Daichi Chikazu⁹, Koutaro Maki¹⁰, Kenji Mishima⁴, Matsuo Yamamoto³, Ryutaro Kamijo¹¹

Affiliations

¹ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan; Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo, Japan.
² Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan. Electronic address: yamadaa@dent.showa-u.ac.jp.
³ Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo, Japan.
⁴ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan.
⁵ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan; Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo, Japan.
⁶ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan.
⁷ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan; Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan.
⁸ Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan.
⁹ Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan.
¹⁰ Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo, Japan.
¹¹ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan.

PMID: 30853186
DOI: 10.1016/j.bbrc.2019.02.106

Abstract

Cdc42 (cell division cycle 42) is ubiquitously expressed small GTPases belonging to the Rho family of proteins. Previously, we generated limb bud mesenchyme-specific Cdc42 inactivated mice (Cdc42 conditional knockout mice; Cdc42^fl/fl; Prx1-Cre), which showed short limbs and cranial bone deformities, though the mechanism related to the cranium phenotype was unclear. In the present study, we investigated the role of Cdc42 in cranial bone development. Our results showed that loss of Cdc42 caused a defect of intramembranous ossification in cranial bone tissues which is related to decreased expressions of cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs). These findings demonstrate that Cdc42 plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.

Keywords: Cdc42; Conditional knockout mice; Osteogenesis; Suture.

Publication types

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

MeSH terms

Animals
Bone Development*
Cranial Sutures / growth & development*
Cranial Sutures / metabolism
Female
Gene Deletion
Gene Expression Regulation, Developmental
Male
Mice
Mice, Knockout
Osteogenesis*
cdc42 GTP-Binding Protein / genetics*
cdc42 GTP-Binding Protein / metabolism

Substances

cdc42 GTP-Binding Protein