{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:44Z","timestamp":1790278844645,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the General Programs of the National Natural Science Foundation of China","award":["82271186"],"award-info":[{"award-number":["82271186"]}]},{"name":"the General Programs of the National Natural Science Foundation of China","award":["81974143"],"award-info":[{"award-number":["81974143"]}]},{"name":"the General Programs of the National Natural Science Foundation of China","award":["2022-PUMCH-C-029"],"award-info":[{"award-number":["2022-PUMCH-C-029"]}]},{"name":"the General Programs of the National Natural Science Foundation of China","award":["7232122"],"award-info":[{"award-number":["7232122"]}]},{"name":"the National High Level Hospital Clinical Research Funding","award":["82271186"],"award-info":[{"award-number":["82271186"]}]},{"name":"the National High Level Hospital Clinical Research Funding","award":["81974143"],"award-info":[{"award-number":["81974143"]}]},{"name":"the National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-C-029"],"award-info":[{"award-number":["2022-PUMCH-C-029"]}]},{"name":"the National High Level Hospital Clinical Research Funding","award":["7232122"],"award-info":[{"award-number":["7232122"]}]},{"name":"the Natural Science Foundation of Beijing, China","award":["82271186"],"award-info":[{"award-number":["82271186"]}]},{"name":"the Natural Science Foundation of Beijing, China","award":["81974143"],"award-info":[{"award-number":["81974143"]}]},{"name":"the Natural Science Foundation of Beijing, China","award":["2022-PUMCH-C-029"],"award-info":[{"award-number":["2022-PUMCH-C-029"]}]},{"name":"the Natural Science Foundation of Beijing, China","award":["7232122"],"award-info":[{"award-number":["7232122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms26031297","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T08:47:57Z","timestamp":1738572477000},"page":"1297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ctdsp2 Knockout Induces Zebrafish Craniofacial Dysplasia via p53 Signaling Activation"],"prefix":"10.3390","volume":"26","author":[{"given":"Xin","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9671-6553","authenticated-orcid":false,"given":"Fuyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eight-Year MD Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1111\/odi.14508","article-title":"The etiology, clinical features, and treatment options of hemifacial microsomia","volume":"29","author":"Luo","year":"2023","journal-title":"Oral Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/ocr.12592","article-title":"Craniofacial microsomia\u2013More than a structural malformation","volume":"26","author":"Suominen","year":"2023","journal-title":"Orthod. 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