Disruption of Distal Appendage Protein CEP164 Causes Skeletal Malformation in Mice

Authors

Hiroyuki Yamaguchi
Megumi Kitami
Margaret Li
Sowmya Swaminathan
Radbod Darabi
Ken-Ichi Takemaru
Yoshihiro Komatsu

Language

English

Publication Date

12-31-2024

Journal

Biochemical and Biophysical Research Communications

DOI

10.1016/j.bbrc.2024.151063

PMID

39612644

PMCID

PMC12011135

PubMedCentral® Posted Date

12-31-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 affected bone development. In contrast, chondrocyte-specific Cep164 deletion did not cause overt skeletal abnormalities, indicating that CEP164 functions in a cell type-specific manner within skeletal tissues. Importantly, Cep164-mutant osteoblasts not only displayed a lack of cilia but also showed an increased number of γH2AX-positive cells, indicating the involvement of defective DNA damage response in the etiology of skeletal lesions of Cep164-mutant mice. These results demonstrate that CEP164 has both ciliary and non-ciliary functions to control osteoblast growth and survival. Our study therefore reveals a novel understanding of the pathogenesis of skeletal ciliopathies associated with CEP164 dysfunction.

Keywords

Animals, Mice, Cilia, Osteoblasts, Bone and Bones, Chondrocytes, Mice, Knockout, DNA Damage, Bone, CEP164, cilia, DNA damage response, mice

Published Open-Access

yes

Recommended Citation

Yamaguchi, Hiroyuki; Kitami, Megumi; Li, Margaret; et al., "Disruption of Distal Appendage Protein CEP164 Causes Skeletal Malformation in Mice" (2024). Faculty, Staff and Student Publications. 6006.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6006