{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:59:52Z","timestamp":1792216792423,"version":"4.4.0"},"reference-count":57,"publisher":"Society for Neuroscience","issue":"2","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":237,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS094559"],"award-info":[{"award-number":["NS094559"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS109790"],"award-info":[{"award-number":["NS109790"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"crossref","award":["84107"],"award-info":[{"award-number":["84107"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"crossref","award":["85200"],"award-info":[{"award-number":["85200"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"crossref","award":["86100"],"award-info":[{"award-number":["86100"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2021,1,13]]},"abstract":"<jats:p>\n                    The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor \u03b1 (HIF\u03b1) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIF\u03b1 in developmental myelination remain incompletely understood. A previous concept proposes that HIF\u03b1 regulates CNS developmental myelination by activating the autocrine Wnt\/\u03b2-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence supporting an alternative understanding of oligodendroglial HIF\u03b1-regulated developmental myelination. At the cellular level, we found that HIF\u03b1 was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIF\u03b1 dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIF\u03b1 played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIF\u03b1-regulated OPC differentiation and myelination. We further identified HIF\u03b1\u2013Sox9 regulatory axis as an underlying molecular mechanism in HIF\u03b1-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIF\u03b1-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIF\u03b1\u2013Sox9 pathway in regulating OPC differentiation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor \u03b1 (HIF\u03b1) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIF\u03b1 in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIF\u03b1-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIF\u03b1-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0731-20.2020","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T17:53:21Z","timestamp":1605722001000},"page":"251-268","source":"Crossref","is-referenced-by-count":19,"title":["HIF\u03b1 Regulates Developmental Myelination Independent of Autocrine Wnt Signaling"],"prefix":"10.1523","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-8999","authenticated-orcid":false,"given":"Sheng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3410-8389","authenticated-orcid":false,"given":"Fuzheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"2023041803445038000_41.2.251.1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.03.003632"},{"key":"2023041803445038000_41.2.251.2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.008441"},{"key":"2023041803445038000_41.2.251.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1718-6"},{"key":"2023041803445038000_41.2.251.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-02-00455.2002"},{"key":"2023041803445038000_41.2.251.5","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000254729.27386.05"},{"key":"2023041803445038000_41.2.251.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.049"},{"key":"2023041803445038000_41.2.251.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.04.009"},{"key":"2023041803445038000_41.2.251.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.016"},{"key":"2023041803445038000_41.2.251.9","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902820204"},{"key":"2023041803445038000_41.2.251.10","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.74"},{"key":"2023041803445038000_41.2.251.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.08.002"},{"key":"2023041803445038000_41.2.251.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.53"},{"key":"2023041803445038000_41.2.251.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.031"},{"key":"2023041803445038000_41.2.251.14","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1806309"},{"key":"2023041803445038000_41.2.251.15","doi-asserted-by":"publisher","DOI":"10.1038\/nn1214-1841a"},{"key":"2023041803445038000_41.2.251.16","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2855"},{"key":"2023041803445038000_41.2.251.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2009.07.010"},{"key":"2023041803445038000_41.2.251.18","doi-asserted-by":"publisher","DOI":"10.1242\/dev.010454"},{"key":"2023041803445038000_41.2.251.19","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22813"},{"key":"2023041803445038000_41.2.251.20","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.152"},{"key":"2023041803445038000_41.2.251.21","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20453"},{"key":"2023041803445038000_41.2.251.22","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3992"},{"key":"2023041803445038000_41.2.251.23","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-013-1314-2"},{"key":"2023041803445038000_41.2.251.24","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21690"},{"key":"2023041803445038000_41.2.251.25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2060-12.2012"},{"key":"2023041803445038000_41.2.251.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.06.009"},{"key":"2023041803445038000_41.2.251.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3467-12.2013"},{"key":"2023041803445038000_41.2.251.28","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095"},{"key":"2023041803445038000_41.2.251.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.024"},{"key":"2023041803445038000_41.2.251.30","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22848"},{"key":"2023041803445038000_41.2.251.31","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2105"},{"key":"2023041803445038000_41.2.251.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4590-13.2014"},{"key":"2023041803445038000_41.2.251.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.04.021"},{"key":"2023041803445038000_41.2.251.34","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-013-1311-5"},{"key":"2023041803445038000_41.2.251.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2482-06.2007"},{"key":"2023041803445038000_41.2.251.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.03.060"},{"key":"2023041803445038000_41.2.251.37","doi-asserted-by":"publisher","DOI":"10.1101\/gad.227785.113"},{"key":"2023041803445038000_41.2.251.38","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23146"},{"key":"2023041803445038000_41.2.251.39","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2646"},{"key":"2023041803445038000_41.2.251.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.021"},{"key":"2023041803445038000_41.2.251.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"2023041803445038000_41.2.251.42","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1408"},{"key":"2023041803445038000_41.2.251.43","first-page":"1951","article-title":"Mouse models of periventricular leukomalacia","volume":"18","author":"Shen","year":"2010","journal-title":"J Vis Exp"},{"key":"2023041803445038000_41.2.251.44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3794-09.2009"},{"key":"2023041803445038000_41.2.251.45","doi-asserted-by":"publisher","DOI":"10.1101\/gad.259003"},{"key":"2023041803445038000_41.2.251.46","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3199-16.2017"},{"key":"2023041803445038000_41.2.251.47","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.19.6739-6749.2003"},{"key":"2023041803445038000_41.2.251.48","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.20"},{"key":"2023041803445038000_41.2.251.49","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh089"},{"key":"2023041803445038000_41.2.251.50","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70294-1"},{"key":"2023041803445038000_41.2.251.51","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2333"},{"key":"2023041803445038000_41.2.251.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.052"},{"key":"2023041803445038000_41.2.251.53","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnmol.2011.00005","article-title":"Oxygen, a key factor regulating cell behavior during neurogenesis and cerebral diseases","volume":"4","author":"Zhang","year":"2011","journal-title":"Front Mol Neurosci"},{"key":"2023041803445038000_41.2.251.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15656-4"},{"key":"2023041803445038000_41.2.251.55","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1035-7"},{"key":"2023041803445038000_41.2.251.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1291-17.2018"},{"key":"2023041803445038000_41.2.251.57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0731-20.2020","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0731-20.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T08:24:41Z","timestamp":1681806281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0731-20.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,18]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1,13]]},"published-print":{"date-parts":[[2021,1,13]]}},"alternative-id":["10.1523\/JNEUROSCI.0731-20.2020"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0731-20.2020","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.30.015131","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.739071567.793580715","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,18]]}}}