{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:16:48Z","timestamp":1790659008732,"version":"4.1.0"},"reference-count":34,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.biologists.com\/user-licence-1-1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2009-0083522"],"award-info":[{"award-number":["2009-0083522"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2015R1A2A1A05001873"],"award-info":[{"award-number":["2015R1A2A1A05001873"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Ras signaling is tightly regulated during neural stem cell (NSC) differentiation, and defects in this pathway result in aberrant brain development. However, the mechanism regulating Ras signaling during NSC differentiation was unknown. Here, we show that stabilized HRas specifically induces neuronal differentiation of NSCs. Lentivirus-mediated HRas overexpression and knockdown resulted in stimulation and inhibition, respectively, of NSC differentiation into neuron in the ex vivo embryo. Retinoic acid, an active metabolite of vitamin A, promoted neuronal differentiation of NSCs by stabilizing HRas, and HRas knockdown blocked the retinoic acid effect. Vitamin-A-deficient mice displayed abnormal brain development with reduced HRas levels and a reduced thickness of the postmitotic region containing differentiated neurons. All of these abnormal phenotypes were rescued with the restoration of HRas protein levels achieved upon feeding with a retinoic-acid-supplemented diet. In summary, this study shows that retinoic acid stabilizes HRas protein during neurogenesis, and that this is required for NSC differentiation into neurons and murine brain development.<\/jats:p>","DOI":"10.1242\/jcs.184366","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:58:28Z","timestamp":1463446708000},"page":"2997-3007","source":"Crossref","is-referenced-by-count":22,"title":["Retinoic-acid-mediated HRas stabilization induces neuronal differentiation of neural stem cells during brain development"],"prefix":"10.1242","volume":"129","author":[{"given":"Jong-Chan","family":"Park","sequence":"first","affiliation":[{"name":"Translational Research Center for Protein Function Control, Yonsei University 1 , Seoul 120-749 , Korea"},{"name":"College of Life Science and Biotechnology, Yonsei University 2 Department of Biotechnology , , Seoul 120-749 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Jeong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Translational Research Center for Protein Function Control, Yonsei University 1 , Seoul 120-749 , Korea"},{"name":"College of Life Science and Biotechnology, Yonsei University 2 Department of Biotechnology , , Seoul 120-749 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Research Center for Protein Function Control, Yonsei University 1 , Seoul 120-749 , Korea"},{"name":"College of Life Science and Biotechnology, Yonsei University 2 Department of Biotechnology , , Seoul 120-749 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DoSik","family":"Min","sequence":"additional","affiliation":[{"name":"Translational Research Center for Protein Function Control, Yonsei University 1 , Seoul 120-749 , Korea"},{"name":"College of Natural Science, Pusan National University 3 Department of Molecular Biology , , Pusan 609-735 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-3276","authenticated-orcid":false,"given":"Kang-Yell","family":"Choi","sequence":"additional","affiliation":[{"name":"Translational Research Center for Protein Function Control, Yonsei University 1 , Seoul 120-749 , Korea"},{"name":"College of Life Science and Biotechnology, Yonsei University 2 Department of Biotechnology , , Seoul 120-749 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061316234767700_JCS184366C1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.seizure.2011.07.013","article-title":"Epilepsy in RAS\/MAPK syndrome: two cases of cardio-facio-cutaneous syndrome with epileptic encephalopathy and a literature review","volume":"21","author":"Adachi","year":"2012","journal-title":"Seizure"},{"key":"2024061316234767700_JCS184366C2","doi-asserted-by":"publisher","first-page":"ra58","DOI":"10.1126\/scisignal.2001936","article-title":"Protein arginine methyltransferase 5 regulates ERK1\/2 signal transduction amplitude and cell fate through CRAF","volume":"4","author":"Andreu-Perez","year":"2011","journal-title":"Sci. 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