{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T22:08:36Z","timestamp":1766182116763,"version":"3.41.2"},"reference-count":40,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Seventh Affiliated Hospital Sun Yat-sen University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR\/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes\u2019 altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.<\/jats:p>","DOI":"10.1242\/bio.059784","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T08:54:46Z","timestamp":1685609686000},"source":"Crossref","is-referenced-by-count":3,"title":["Loss of <i>flrt2<\/i> gene leads to microphthalmia in zebrafish"],"prefix":"10.1242","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-7915","authenticated-orcid":false,"given":"Siyu","family":"Yang","sequence":"first","affiliation":[{"name":"The Seventh Affiliated Hospital of Sun Yat-Sen University 1 Department of Ophthalmology , , Shenzhen, 518107 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5608-6101","authenticated-orcid":false,"given":"Lianggui","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University 2 , Guangzhou, 510060 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-6205","authenticated-orcid":false,"given":"Huiling","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University 2 , Guangzhou, 510060 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-8944","authenticated-orcid":false,"given":"Jingyi","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University 2 , Guangzhou, 510060 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyue","family":"Liu","sequence":"additional","affiliation":[{"name":"China Zebrafish Resource Center, National Aquatic Biological Resource Center, Institute of Hydrobiology, Chinese Academy of Sciences 3 , Wuhan, 430072 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University 2 , Guangzhou, 510060 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-5245","authenticated-orcid":false,"given":"Mingzhe","family":"Cao","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital of Sun Yat-Sen University 1 Department of Ophthalmology , , Shenzhen, 518107 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"2023061508444700800_BIO059784C1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s12576-015-0416-1","article-title":"Ion channels, guidance molecules, intracellular signaling and transcription factors regulating nervous and vascular system development","volume":"66","author":"Akita","year":"2016","journal-title":"J. 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