Piezo1 mutant zebrafish as a model of idiopathic scoliosis

Ramli; Toshihiro Aramaki; Masakatsu Watanabe; Shigeru Kondo

doi:10.3389/fgene.2023.1321379

Piezo1 mutant zebrafish as a model of idiopathic scoliosis

Front Genet. 2024 Jan 8:14:1321379. doi: 10.3389/fgene.2023.1321379. eCollection 2023.

Authors

Ramli¹, Toshihiro Aramaki^{1

2}, Masakatsu Watanabe¹, Shigeru Kondo¹

Affiliations

¹ Laboratory of Pattern Formation, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
² Japan Science and Technology Agency, PRESTO, Tokyo, Japan.

Abstract

Scoliosis is a condition where the spine curves sideways, unique to humans due to their upright posture. However, the cause of this disease is not well understood because it is challenging to find a model for experimentation. This study aimed to create a model for human idiopathic scoliosis by manipulating the function of mechanosensitive channels called Piezo channels in zebrafish. Zebrafish were chosen because they experience similar biomechanical forces to humans, particularly in relation to the role of mechanical force in scoliosis progression. Here we describe piezo1 and piezo2a are involved in bone formation, with a double knockout resulting in congenital systemic malformations. However, an in-frame mutation of piezo1 led to fully penetrant juvenile-onset scoliosis, bone asymmetry, reduced tissue mineral density, and abnormal intervertebral discs-resembling non-congenital scoliosis symptoms in humans. These findings suggest that functional Piezo channels responding to mechanical forces are crucial for bone formation and maintaining spine integrity, providing insights into skeletal disorders.

Keywords: Piezo channel; TMD; idiopathic scoliosis; vertebral bone; zebrafish.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Grant-in-Aid for Transformative Research Areas (20H05943), Grant-in-Aid for Scientific Research (19H00994), The Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, JSPS KAKENHI Grant Number JP16K14736 and JST PRESTO JPMJPR2042.