{"title":"Anp32b-deficiency suppresses ocular development by repression of Pax6.","authors":"Yu-Sheng Wei, Hao-Ran Liu, Qian Yang, Zhe Zhi, Yun Yu","doi":"10.1159/000542447","DOIUrl":null,"url":null,"abstract":"<p><p>Introduction This study aims to elucidate the role and molecular mechanisms of acidic leucine-rich nuclear phosphoprotein 32kDa B (Anp32b)-deficiency in ocular development. Methods We used constitutive C57BL/6-derived Anp32b-/- mice to elucidate the role of Anp32b in ocular development, including the phenotype and proportion of eye malformation in different genotypes. RNA-Seq analysis and rescue experiments were performed to investigate the underlying mechanisms of Anp32b. Results Deletion of Anp32b contributes to severe defects in ocular development, including anophthalmia and microphthalmia. Moreover, Anp32b is highly expressed in the lens, and Anp32b-/- embryos with microphthalmia often exhibit severely impaired lens development. Mechanistically, ANP32B directly interacts with paired box protein 6 (PAX6), a master transcriptional regulator, and enhances its transcriptional activity. Overexpression of PAX6 partially but significantly reverses the inhibition of proliferation observed in ANP32B knockdown lens epithelial cells. Conclusions Our findings indicate that Anp32b-deficiency suppresses ocular development by repressing Pax6 and identify that Anp32b is a viable therapeutic target for ocular developmental defects.</p>","PeriodicalId":19662,"journal":{"name":"Ophthalmic Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.0000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmic Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000542447","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction This study aims to elucidate the role and molecular mechanisms of acidic leucine-rich nuclear phosphoprotein 32kDa B (Anp32b)-deficiency in ocular development. Methods We used constitutive C57BL/6-derived Anp32b-/- mice to elucidate the role of Anp32b in ocular development, including the phenotype and proportion of eye malformation in different genotypes. RNA-Seq analysis and rescue experiments were performed to investigate the underlying mechanisms of Anp32b. Results Deletion of Anp32b contributes to severe defects in ocular development, including anophthalmia and microphthalmia. Moreover, Anp32b is highly expressed in the lens, and Anp32b-/- embryos with microphthalmia often exhibit severely impaired lens development. Mechanistically, ANP32B directly interacts with paired box protein 6 (PAX6), a master transcriptional regulator, and enhances its transcriptional activity. Overexpression of PAX6 partially but significantly reverses the inhibition of proliferation observed in ANP32B knockdown lens epithelial cells. Conclusions Our findings indicate that Anp32b-deficiency suppresses ocular development by repressing Pax6 and identify that Anp32b is a viable therapeutic target for ocular developmental defects.
期刊介绍:
''Ophthalmic Research'' features original papers and reviews reporting on translational and clinical studies. Authors from throughout the world cover research topics on every field in connection with physical, physiologic, pharmacological, biochemical and molecular biological aspects of ophthalmology. This journal also aims to provide a record of international clinical research for both researchers and clinicians in ophthalmology. Finally, the transfer of information from fundamental research to clinical research and clinical practice is particularly welcome.