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Volume 14
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10.3390/genes14040838
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Article

vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway

by
Xiaomin Niu
1,
Fuyu Zhang
2,
Lu Ping
2,
Yibei Wang
3,
Bo Zhang
4,
Jian Wang
1 and
Xiaowei Chen
1,*
1
Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2
8-Year MD Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
3
Department of Otolaryngology-Head & Neck Surgery, China-Japan Friendship Hospital, Beijing 100730, China
4
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100730, China
*
Author to whom correspondence should be addressed.
Genes 2023, 14(4), 838; https://doi.org/10.3390/genes14040838
Submission received: 26 February 2023 / Revised: 20 March 2023 / Accepted: 28 March 2023 / Published: 30 March 2023
(This article belongs to the Special Issue Zebrafish Models for Human Genetic Disease Studies)
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Abstract

Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to the pathogenesis of HFM is largely unknown. Here, we sought to elucidate the effects of the VWA1 mutation at the molecular level by generating a vwa1-knockout zebrafish line using CRISPR/Cas9. Mutants and crispants showed cartilage dysmorphologies, including hypoplastic Meckel’s cartilage and palatoquadrate cartilage, malformed ceratohyal with widened angle, and deformed or absent ceratobranchial cartilages. Chondrocytes exhibited a smaller size and aspect ratio and were aligned irregularly. In situ hybridization and RT-qPCR showed a decrease in barx1 and col2a1a expression, indicating abnormal cranial neural crest cell (CNCC) condensation and differentiation. CNCC proliferation and survival were also impaired in the mutants. Expression of FGF pathway components, including fgf8a, fgfr1, fgfr2, fgfr3, fgfr4, and runx2a, was decreased, implying a role for VWA1 in regulating FGF signaling. Our results demonstrate that VWA1 is essential for zebrafish chondrogenesis through effects on condensation, differentiation, proliferation, and apoptosis of CNCCs, and likely impacts chondrogenesis through regulation of the FGF pathway.
Keywords: hemifacial microsomia; VWA1; FGF pathway; cranial neural crest cells hemifacial microsomia; VWA1; FGF pathway; cranial neural crest cells

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MDPI and ACS Style

Niu, X.; Zhang, F.; Ping, L.; Wang, Y.; Zhang, B.; Wang, J.; Chen, X. vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway. Genes 2023, 14, 838. https://doi.org/10.3390/genes14040838

AMA Style

Niu X, Zhang F, Ping L, Wang Y, Zhang B, Wang J, Chen X. vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway. Genes. 2023; 14(4):838. https://doi.org/10.3390/genes14040838

Chicago/Turabian Style

Niu, Xiaomin, Fuyu Zhang, Lu Ping, Yibei Wang, Bo Zhang, Jian Wang, and Xiaowei Chen. 2023. "vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway" Genes 14, no. 4: 838. https://doi.org/10.3390/genes14040838

APA Style

Niu, X., Zhang, F., Ping, L., Wang, Y., Zhang, B., Wang, J., & Chen, X. (2023). vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway. Genes, 14(4), 838. https://doi.org/10.3390/genes14040838

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