{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:16:27Z","timestamp":1792214187371,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T00:00:00Z","timestamp":1617580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"CAMS Innovation Fund for Medical Science","award":["2017-I2M-1-004"],"award-info":[{"award-number":["2017-I2M-1-004"]}]},{"name":"CAMS Innovation Fund for Medical Science","award":["2016-I2M-1-004"],"award-info":[{"award-number":["2016-I2M-1-004"]}]},{"name":"CAMS Innovation Fund for Medical Science","award":["2016-I2M-2-001"],"award-info":[{"award-number":["2016-I2M-2-001"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0902502"],"award-info":[{"award-number":["2016YFC0902502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFA0100702"],"award-info":[{"award-number":["2016YFA0100702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970772"],"award-info":[{"award-number":["31970772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Wnt\/\u03b2-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of neural progenitors in a context-dependent manner and affects neocortex layer formation. However, the specific role of Wnt\/\u03b2-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt\/\u03b2-catenin signaling, colocalizes with \u03b2-catenin at the endfeet of radial glia in the ventricular zone of embryo mouse neocortex. Overexpression and knockdown of Zbed3 increased and decreased the activity of Wnt\/\u03b2-catenin signaling in the neocortex, respectively. Interestingly, knockdown of Zbed3 in vivo could significantly shift neuronal fates from deep layers to upper layers but is not required for the proliferation and differentiation of neural progenitors. Overexpression of Zbed3 led to increased generation of deep-layer neurons without impairing cell cycle exit of neural progenitors. More importantly, knockdown of Zbed3 could effectively block the effects of the ectopic expression of stabilized \u03b2-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt\/\u03b2-catenin signaling regulating neuronal layer fates in the developing brain.<\/jats:p>","DOI":"10.1093\/cercor\/bhab070","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T12:10:43Z","timestamp":1615205443000},"page":"4078-4091","source":"Crossref","is-referenced-by-count":10,"title":["Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain"],"prefix":"10.1093","volume":"31","author":[{"given":"Xiangbin","family":"Ruan","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoao","family":"Liu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Chen","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjie","family":"Sun","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Hou","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yin","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boqin","family":"Qiang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Shu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhong","family":"Peng","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Institute of Medical Biology of the Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"issue":"2","key":"2021080216410080700_ref1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2004.12.036","article-title":"Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo","volume":"45","author":"Arlotta","year":"2005","journal-title":"Neuron"},{"issue":"11","key":"2021080216410080700_ref2","doi-asserted-by":"crossref","first-page":"6683","DOI":"10.1074\/jbc.M807753200","article-title":"Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel Axin-interacting protein that activates Wnt\/beta-catenin signaling","volume":"284","author":"Chen","year":"2009","journal-title":"J Biol Chem"},{"issue":"5580","key":"2021080216410080700_ref3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1126\/science.1074192","article-title":"Regulation of cerebral cortical size by control of cell cycle exit in neural precursors","volume":"297","author":"Chenn","year":"2002","journal-title":"Science"},{"issue":"5","key":"2021080216410080700_ref4","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1242\/dev.104505","article-title":"Activated retinoid receptors are required for the migration and fate maintenance of subsets of cortical neurons","volume":"141","author":"Choi","year":"2014","journal-title":"Development"},{"issue":"7069","key":"2021080216410080700_ref5","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nature04170","article-title":"Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction","volume":"438","author":"Davidson","year":"2005","journal-title":"Nature"},{"issue":"11","key":"2021080216410080700_ref6","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1093\/cercor\/bhs252","article-title":"POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex","volume":"23","author":"Dominguez","year":"2013","journal-title":"Cereb Cortex"},{"issue":"1","key":"2021080216410080700_ref7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/stem.1820","article-title":"Wnt\/beta-catenin signaling regulates sequential fate decisions of murine cortical precursor cells","volume":"33","author":"Draganova","year":"2015","journal-title":"Stem Cells"},{"issue":"4","key":"2021080216410080700_ref8","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.neuron.2013.06.017","article-title":"Axin directs the amplification and differentiation of intermediate progenitors in the developing cerebral cortex","volume":"79","author":"Fang","year":"2013","journal-title":"Neuron"},{"issue":"38","key":"2021080216410080700_ref9","doi-asserted-by":"crossref","first-page":"13613","DOI":"10.1523\/JNEUROSCI.3120-11.2011","article-title":"Cdk5-mediated phosphorylation of Axin directs axon formation during cerebral cortex development","volume":"31","author":"Fang","year":"2011","journal-title":"J Neurosci"},{"issue":"1","key":"2021080216410080700_ref10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/jmcb\/mjx035","article-title":"Zbed3 participates in the subcortical maternal complex and regulates the distribution of organelles","volume":"10","author":"Gao","year":"2018","journal-title":"J Mol Cell Biol"},{"issue":"12","key":"2021080216410080700_ref11","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1523\/JNEUROSCI.14-12-07319.1994","article-title":"The T-alpha-1 alpha-tubulin promoter specifies gene-expression as a function of neuronal growth and regeneration in transgenic mice","volume":"14","author":"Gloster","year":"1994","journal-title":"J Neurosci"},{"issue":"11","key":"2021080216410080700_ref12","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrn3586","article-title":"Molecular logic of neocortical projection neuron specification, development and diversity","volume":"14","author":"Greig","year":"2013","journal-title":"Nat Rev Neurosci"},{"issue":"2","key":"2021080216410080700_ref13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nn.3917","article-title":"The neocortical circuit: themes and variations","volume":"18","author":"Harris","year":"2015","journal-title":"Nat Neurosci"},{"issue":"7","key":"2021080216410080700_ref14","doi-asserted-by":"crossref","first-page":"a008094","DOI":"10.1101\/cshperspect.a008094","article-title":"Wnt signaling and forebrain development","volume":"4","author":"Harrison-Uy","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"12","key":"2021080216410080700_ref15","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1242\/dev.01165","article-title":"The Wnt\/\u03b2-catenin pathway directs neuronal differentiation of cortical neural precursor cells","volume":"131","author":"Hirabayashi","year":"2004","journal-title":"Development"},{"key":"2021080216410080700_ref16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0092-8674(01)00465-2","article-title":"Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny","volume":"106","author":"Isshiki","year":"2001","journal-title":"Cell"},{"key":"2021080216410080700_ref17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1097-2765(01)00224-6","article-title":"Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway","volume":"7","author":"Mao","year":"2001","journal-title":"Mol Cell"},{"issue":"12","key":"2021080216410080700_ref18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nrn3618","article-title":"Temporal fate specification and neural progenitor competence during development","volume":"14","author":"Kohwi","year":"2013","journal-title":"Nat Rev Neurosci"},{"key":"2021080216410080700_ref19","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nrn2008","article-title":"Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion","volume":"7","author":"Kriegstein","year":"2006","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"2021080216410080700_ref20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/jb\/mvw072","article-title":"Context-dependent regulation of the \u03b2-catenin transcriptional complex supports diverse functions of Wnt\/\u03b2-catenin signaling","volume":"161","author":"Masuda","year":"2017","journal-title":"J Biochem"},{"issue":"2","key":"2021080216410080700_ref21","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1523\/JNEUROSCI.4131-10.2011","article-title":"Tbr1 and Fezf2 regulate alternate corticofugal neuronal identities during neocortical development","volume":"31","author":"McKenna","year":"2011","journal-title":"J Neurosci"},{"issue":"37","key":"2021080216410080700_ref22","doi-asserted-by":"crossref","first-page":"11702","DOI":"10.1073\/pnas.1504144112","article-title":"Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex","volume":"112","author":"McKenna","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2021080216410080700_ref23","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nrn2151","article-title":"Neuronal subtype specification in the cerebral cortex","volume":"8","author":"Molyneaux","year":"2007","journal-title":"Nat Rev Neurosci"},{"issue":"5","key":"2021080216410080700_ref24","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1523\/JNEUROSCI.5404-10.2011","article-title":"Wnt signaling regulates neuronal differentiation of cortical intermediate progenitors","volume":"31","author":"Munji","year":"2011","journal-title":"J Neurosci"},{"issue":"43","key":"2021080216410080700_ref25","doi-asserted-by":"crossref","first-page":"13710","DOI":"10.1523\/JNEUROSCI.3022-09.2009","article-title":"Beta-catenin signaling levels in progenitors influence the laminar cell fates of projection neurons","volume":"29","author":"Mutch","year":"2009","journal-title":"J Neurosci"},{"issue":"10","key":"2021080216410080700_ref26","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1093\/cercor\/bhr317","article-title":"Cell type-specific three-dimensional structure of thalamocortical circuits in a column of rat vibrissal cortex","volume":"22","author":"Oberlaender","year":"2012","journal-title":"Cereb Cortex"},{"issue":"6","key":"2021080216410080700_ref27","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/nprot.2007.153","article-title":"Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections","volume":"2","author":"Obernosterer","year":"2007","journal-title":"Nat Protoc"},{"issue":"7774","key":"2021080216410080700_ref28","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/s41586-019-1515-6","article-title":"Temporal plasticity of apical progenitors in the developing mouse neocortex","volume":"573","author":"Oberst","year":"2019","journal-title":"Nature"},{"issue":"10","key":"2021080216410080700_ref29","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nrn2719","article-title":"Evolution of the neocortex: a perspective from developmental biology","volume":"10","author":"Rakic","year":"2009","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"2021080216410080700_ref30","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1038\/nprot.2006.276","article-title":"In vivo electroporation in the embryonic mouse central nervous system","volume":"1","author":"Saito","year":"2006","journal-title":"Nat Protoc"},{"issue":"5","key":"2021080216410080700_ref31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.devcel.2019.04.017","article-title":"Opposing gradients of microRNA expression temporally pattern layer formation in the developing neocortex","volume":"49","author":"Shu","year":"2019","journal-title":"Dev Cell"},{"key":"2021080216410080700_ref32","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/18884","article-title":"Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells","volume":"398","author":"Tetsu","year":"1999","journal-title":"Nature"},{"issue":"48","key":"2021080216410080700_ref33","doi-asserted-by":"crossref","first-page":"12620","DOI":"10.1523\/JNEUROSCI.3180-06.2006","article-title":"Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation","volume":"26","author":"Woodhead","year":"2006","journal-title":"J Neurosci"},{"key":"2021080216410080700_ref34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3389\/fncel.2015.00217","article-title":"Emerging roles of Axin in cerebral cortical development","volume":"9","author":"Ye","year":"2015","journal-title":"Front Cell Neurosci"},{"issue":"7069","key":"2021080216410080700_ref35","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nature04185","article-title":"A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation","volume":"438","author":"Zeng","year":"2005","journal-title":"Nature"},{"issue":"4","key":"2021080216410080700_ref36","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.neuroscience.2006.07.007","article-title":"Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway","volume":"142","author":"Zhou","year":"2006","journal-title":"Neuroscience"}],"container-title":["Cerebral Cortex"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cercor\/article-pdf\/31\/9\/4078\/39376862\/bhab070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cercor\/article-pdf\/31\/9\/4078\/39376862\/bhab070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T19:27:49Z","timestamp":1627932469000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cercor\/article\/31\/9\/4078\/6210044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,5]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,4,5]]},"published-print":{"date-parts":[[2021,7,29]]}},"URL":"https:\/\/doi.org\/10.1093\/cercor\/bhab070","relation":{},"ISSN":["1047-3211","1460-2199"],"issn-type":[{"value":"1047-3211","type":"print"},{"value":"1460-2199","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9]]},"published":{"date-parts":[[2021,4,5]]}}}