PUBLICATION
ctdsp2 Knockout Induces Zebrafish Craniofacial Dysplasia via p53 Signaling Activation
- Authors
- Xia, X., Song, W., Zhang, F., Fan, Y., Zhang, B., Chen, X.
- ID
- ZDB-PUB-250214-8
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Chen, Xiaowei, Xia, Xin, Zhang, Bo, Zhang, Fuyu
- Keywords
- craniofacial defects, ctdsp2, neural crest cell, p53 signaling pathway, zebrafish
- MeSH Terms
-
- Cell Proliferation
- Gene Knockout Techniques
- Animals
- Cell Differentiation/genetics
- Neural Crest/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Apoptosis*/genetics
- Craniofacial Abnormalities*/etiology
- Craniofacial Abnormalities*/genetics
- Craniofacial Abnormalities*/metabolism
- Craniofacial Abnormalities*/pathology
- Signal Transduction*
- Gene Expression Regulation, Developmental
- Chondrocytes/metabolism
- Chondrocytes/pathology
- Tumor Suppressor Protein p53*/genetics
- Tumor Suppressor Protein p53*/metabolism
- PubMed
- 39941065 Full text @ Int. J. Mol. Sci.
Citation
Xia, X., Song, W., Zhang, F., Fan, Y., Zhang, B., Chen, X. (2025) ctdsp2 Knockout Induces Zebrafish Craniofacial Dysplasia via p53 Signaling Activation. International Journal of Molecular Sciences. 26:.
Abstract
Hemifacial microsomia (HFM) is a rare congenital craniofacial deformity that significantly impacts the appearance and hearing. The genetic etiology of HFM remains largely unknown, although genetic factors are considered to be primary contributors. We previously identified CTDSP2 as a potential causative gene in HFM cases. Utilizing CRISPR/Cas9, we knocked out ctdsp2 in zebrafish and analyzed the spatiotemporal expression of ctdsp2 and neural crest cell (NCC) markers through in situ hybridization (ISH). Craniofacial cartilage and chondrocyte phenotypes were visualized using Alcian blue and wheat germ agglutinin (WGA) staining. Cell proliferation and apoptosis were assessed via immunofluorescence with PH3 and TUNEL. RNA sequencing was performed on ctdsp2-/- embryos and control siblings, followed by rescue experiments. Knockout of ctdsp2 in zebrafish resulted in craniofacial defects characteristic of HFM. We observed abnormalities in NCC apoptosis and proliferation in the pharyngeal arches, as well as impaired differentiation of chondrocytes in ctdsp2-/- embryos. RNA-Seq analysis revealed significantly higher expression of genes in the p53 signaling pathway in mutants. Furthermore, ctdsp2 mRNA injection and tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia. Our findings suggest that ctdsp2 knockout induces zebrafish craniofacial dysplasia, primarily by disrupting pharyngeal chondrocyte differentiation and inhibiting NCC proliferation through p53 signaling pathway activation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping