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Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies to alleviate aging-associated neurological diseases. In this study, we investigated the role of aging-related genes in brain vascular development using zebrafish as an in vivo model. By thoroughly analyzing scRNA-seq datasets of mid- and old-aged brain vascular endothelial cells (human\/mouse), we found ribosomal protein S20 (rps20) significantly down-regulated during aging. qPCR analysis and whole-mount in situ hybridization validated a high expression of rps20 during early zebrafish development, which progressively decreased in adult and aged zebrafish brains. Functional studies using the CRISPR\/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos. In conclusion, our findings demonstrate that rps20 is essential for proper brain vascular development and the maintenance of vascular homeostasis in zebrafish, revealing a novel mechanism by which aging-related genes regulate brain vascular development. This study provides new insights that may aid in understanding and treating aging-associated vascular malformations and neurological pathologies.<\/jats:p>","DOI":"10.3390\/cells14141070","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:54:23Z","timestamp":1752479663000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of Hindbrain Vascular Development by rps20 in Zebrafish"],"prefix":"10.3390","volume":"14","author":[{"given":"Xinyu","family":"Shen","sequence":"first","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhi","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunze","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2764-6544","authenticated-orcid":false,"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3621-0994","authenticated-orcid":false,"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00441-003-0739-8","article-title":"Interdependent development of blood vessels and organs","volume":"314","author":"Nikolova","year":"2003","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1016\/j.cell.2024.07.012","article-title":"A systems view of the vascular endothelium in health and disease","volume":"187","author":"Augustin","year":"2024","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1016\/j.jacc.2023.11.007","article-title":"Global Burden of Cardiovascular Diseases and Risks, 1990-2022","volume":"82","author":"Mensah","year":"2023","journal-title":"J. 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