{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T05:25:19Z","timestamp":1777267519646,"version":"3.51.4"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["ZIAHD008988"],"award-info":[{"award-number":["ZIAHD008988"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Development"],"abstract":"<jats:p>Niemann-Pick disease type C (NPC) is a rare, fatal, neurodegenerative lysosomal disease caused by mutations of either <jats:italic>NPC1<\/jats:italic> or <jats:italic>NPC2<\/jats:italic>. NPC2 is a soluble lysosomal protein which functions in coordination with NPC1 to efflux cholesterol from the lysosomal compartment. Mutations of either gene result in the accumulation of unesterified cholesterol and other lipids in the late endosome\/lysosome, while reducing cellular cholesterol bioavailability. Zygotic null <jats:italic>npc2<\/jats:italic><jats:sup><jats:italic>m\/m<\/jats:italic><\/jats:sup> zebrafish showed significant unesterified cholesterol accumulation at larval stages, a reduction in body size, and motor and balance defects in adulthood. However, the phenotype at embryonic stages was milder than expected, suggesting a possible role of maternal Npc2 in embryonic development. Maternal-zygotic <jats:italic>npc2<\/jats:italic><jats:sup><jats:italic>m\/m<\/jats:italic><\/jats:sup> zebrafish exhibited significant developmental defects including defective otic vesicle development\/absent otoliths, abnormal head\/brain development, curved\/twisted body axes, no circulating blood cells, and died by 72 hpf. RNA-seq analysis conducted on 30 hpf <jats:italic>npc2<\/jats:italic><jats:sup>+<jats:italic>\/m<\/jats:italic><\/jats:sup> and MZ<jats:italic>npc2<\/jats:italic><jats:sup><jats:italic>m\/m<\/jats:italic><\/jats:sup> embryos revealed a significant reduction in the expression of <jats:italic>notch3<\/jats:italic> and other downstream genes in the Notch signaling pathway, suggesting that impaired Notch3 signaling underlies aspects of the developmental defects observed in MZ<jats:italic>npc2<\/jats:italic><jats:sup><jats:italic>m\/m<\/jats:italic><\/jats:sup> zebrafish.<\/jats:p>","DOI":"10.1242\/dev.194258","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T15:30:14Z","timestamp":1615822214000},"page":"dev.194258","source":"Crossref","is-referenced-by-count":10,"title":["The role of Niemann-Pick type C2 in zebrafish embryonic development"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-4482","authenticated-orcid":false,"given":"Wei-Chia","family":"Tseng","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana J","family":"Johnson Escauriza","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chon-Hwa","family":"Tsai-Morris","sequence":"additional","affiliation":[{"name":"Zebrafish Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4838-8641","authenticated-orcid":false,"given":"Benjamin","family":"Feldman","sequence":"additional","affiliation":[{"name":"Zebrafish Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-3744","authenticated-orcid":false,"given":"Ryan K.","family":"Dale","sequence":"additional","affiliation":[{"name":"Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2524-1420","authenticated-orcid":false,"given":"Christopher A.","family":"Wassif","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0046","authenticated-orcid":false,"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,3,15]]},"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dev.194258","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dev.194258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T15:30:14Z","timestamp":1615822214000},"score":1,"resource":{"primary":{"URL":"http:\/\/dev.biologists.org\/lookup\/doi\/10.1242\/dev.194258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":0,"alternative-id":["10.1242\/dev.194258"],"URL":"https:\/\/doi.org\/10.1242\/dev.194258","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]}}}