{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:32Z","timestamp":1785434912321,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82271186"],"award-info":[{"award-number":["82271186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82271186"],"award-info":[{"award-number":["82271186"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>Microtia\u2013atresia is a rare craniofacial malformation primarily affecting the first and second pharyngeal arches, leading to the deformity of the auricle and atresia of the external ear canal. Its etiology is heterogenous and largely unknown, including both genetic and environmental factors. The HOXA4 gene has been identified as potentially pathogenetic for microtia\u2013atresia in three twin families. A hoxa4a mosaic knockdown zebrafish model was constructed using CRISPR\/Cas9. hoxa4a was expressed in the mandible during early development in zebrafish, while the F0 mosaic knockdowns exhibited craniofacial malformations with abnormal chondrocyte morphologies. Specifically, hoxa4a knockdown reduced cranial neural crest cell proliferation while increasing apoptosis, markedly downregulating chondrogenic markers sox9a and col2a1a. Consequently, pharyngeal arch chondrocytes exhibited disorganized arrangement and morphological abnormalities, resulting in mandibular hypoplasia. Our findings provide important insights into the role of hoxa4a in zebrafish mandibular development and the pathology of microtia\u2013atresia caused by HOXA4 gene mutations in humans.<\/jats:p>","DOI":"10.3390\/jdb14020022","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:19:29Z","timestamp":1778854769000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional and Genetic Analyses Unveil the Implication of hoxa4a in Zebrafish Craniofacial Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Le","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 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":"8-Year MD Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6114-1768","authenticated-orcid":false,"given":"Ruzhen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-5629","authenticated-orcid":false,"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 Otorhinolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1080\/00016489.2023.2279263","article-title":"Congenital ear malformation (CEM)","volume":"143","author":"Zou","year":"2023","journal-title":"Acta Otolaryngol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1055\/s-0035-1568139","article-title":"Congenital Auricular Malformations: Description of Anomalies and Syndromes","volume":"31","year":"2015","journal-title":"Facial Plast. 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