{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:08:52Z","timestamp":1753891732078,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>myo7aa<\/jats:italic>, the homolog of the human Usher 1B syndrome pathogenic gene, <jats:italic>myo7A<\/jats:italic>, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that <jats:italic>myo7aa<\/jats:italic> regulate hearing and balance still need to be studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we generated two independent zebrafish <jats:italic>myo7aa<\/jats:italic> knockout lines using CRISPR\/Cas9 technology. To investigate the effects of <jats:italic>myo7aa<\/jats:italic> on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which <jats:italic>myo7aa<\/jats:italic> affects hearing, transcriptome sequencing and bioinformatics analysis were employed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study showed that hair cells of <jats:italic>myo7aa<\/jats:italic>-\/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in <jats:italic>myo7aa<\/jats:italic>-\/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in <jats:italic>myo7aa<\/jats:italic>-\/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in <jats:italic>myo7aa<\/jats:italic> knockout zebrafish.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest that zebrafish <jats:italic>myo7aa<\/jats:italic> affects congenital hearing by regulating Rho GTPase signaling, and loss of <jats:italic>myo7aa<\/jats:italic> leads to abnormal Rho GTPase signaling and impairs hair cell function. <jats:italic>myo7aa<\/jats:italic>, <jats:italic>myo7A<\/jats:italic>, arhgap33, dab2ip, arghef40 and <jats:italic>myo7aa<\/jats:italic>-\/- fonts in the abstract are italicized. -\/- is a superscript format.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2024.1405109","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T16:29:57Z","timestamp":1721060997000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Binling","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinghua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganghua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanjia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangding","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruosha","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6031","DOI":"10.1021\/bi00320a020","article-title":"Association of microtubules and neurofilaments in vitro is not mediated by ATP","volume":"23","author":"Aamodt","year":"1984","journal-title":"Biochemistry"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13465","DOI":"10.1074\/jbc.M116.716407","article-title":"EHD3 protein is required for tubular recycling endosome stabilization, and an asparagine-glutamic acid residue pair within its Eps15 homology (EH) domain dictates its selective binding to NPF peptides","volume":"291","author":"Bahl","year":"2016","journal-title":"J. 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