{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:20Z","timestamp":1787005760487,"version":"build-2736575974"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"17","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R21NS133390-01"],"award-info":[{"award-number":["1R21NS133390-01"]}],"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":["1R21NS117848-01"],"award-info":[{"award-number":["1R21NS117848-01"]}],"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":["1R21NS138661-01"],"award-info":[{"award-number":["1R21NS138661-01"]}],"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":["5R01NS122902-03"],"award-info":[{"award-number":["5R01NS122902-03"]}],"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":["5R37NS095733-09"],"award-info":[{"award-number":["5R37NS095733-09"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["28956"],"award-info":[{"award-number":["28956"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:p>The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human PCs retain proliferative marker expression weeks after leaving the VZ, another feature not observed in rodents. Human PC maturation is protracted with an extensive migration and reorganization throughout development with dendritic arborization developing in late gestation. We define a continuous transcriptional cascade of PC development from neuroepithelial cells to mature PCs. In contrast, while human interneuronal progenitors are born beginning in early fetal development, they exhibit an even more protracted differentiation across late gestation and into postnatal ages. These findings show dynamic developmental process for human cerebellar GABAergic neurons and underscore the importance of the embryonic environment, with early disruptions having potentially significant impacts.<\/jats:p>","DOI":"10.1073\/pnas.2415425122","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T13:45:56Z","timestamp":1744983956000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Mapping the developmental profile of ventricular zone\u2013derived neurons in the human cerebellum"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6134-7812","authenticated-orcid":false,"given":"Anders W.","family":"Erickson","sequence":"first","affiliation":[{"name":"The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children","place":["Toronto, Canada"]},{"name":"Developmental and Stem Cell Biology Program, The Hospital for Sick Children","place":["Toronto, Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3600-9279","authenticated-orcid":false,"given":"Henry","family":"Tan","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam D.","family":"Hendrikse","sequence":"additional","affiliation":[{"name":"The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children","place":["Toronto, Canada"]},{"name":"Developmental and Stem Cell Biology Program, The Hospital for Sick Children","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-1346","authenticated-orcid":false,"given":"Jake","family":"Millman","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Thomson","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Golser","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Khan","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9786-4333","authenticated-orcid":false,"given":"Guanyi","family":"He","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Bach","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpit Suresh","family":"Mishra","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janja","family":"Kopic","sequence":"additional","affiliation":[{"name":"Croatian Institute for Brain Research, School of Medicine, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5238-6820","authenticated-orcid":false,"given":"Zeljka","family":"Krsnik","sequence":"additional","affiliation":[{"name":"Croatian Institute for Brain Research, School of Medicine, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferechte","family":"Encha-Razavi","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Necker-Enfants Malades","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Petrilli","sequence":"additional","affiliation":[{"name":"H\u00f4pital Robert-Debr\u00e9, INSERM UMR 1141","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-9538","authenticated-orcid":false,"given":"Fabien","family":"Guimiot","sequence":"additional","affiliation":[{"name":"H\u00f4pital Robert-Debr\u00e9, INSERM UMR 1141","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Surgical Pathology Unit, San Camillo Forlanini Hospital","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-8911","authenticated-orcid":false,"given":"Kimberly A.","family":"Aldinger","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]},{"name":"Department of Neurology, University of Washington","place":["Seattle"]},{"name":"Department of Pediatrics, University of Washington","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["Toronto, Canada"]},{"name":"Texas Children\u2019s Cancer and Hematology Center","place":["Houston"]},{"name":"Department of Pediatrics\u2014Hematology\/Oncology, Baylor College of Medicine","place":["Houston"]},{"name":"Department of Neurosurgery, Baylor College of Medicine","place":["Houston"]},{"name":"Department of Neurosurgery, Texas Children\u2019s Hospital","place":["Houston"]},{"name":"Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine","place":["Houston"]},{"name":"The Arthur and Sonia Labatt Brain Tumour Research Centre and the Developmental and Stem Cell Biology Program, The Hospital for Sick Children","place":["Toronto, Canada"]},{"name":"Department of Surgery, University of Toronto","place":["Toronto, Canada"]},{"name":"Department of Medical Biophysics, University of Toronto","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9978-675X","authenticated-orcid":false,"given":"Kathleen J.","family":"Millen","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]},{"name":"Department of Pediatrics, University of Washington","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-8683","authenticated-orcid":false,"given":"Parthiv","family":"Haldipur","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Center for Integrative Brain Research","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0479-11.2011"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-111020-091953"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax7526"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02355-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05215-w"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05208-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05578-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1506-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4337"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605699104"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315024111"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2526-15.2016"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-008-0079-z"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0957-09.2009"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.10.008"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-014-0596-x"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj1598"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30977-2"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3656-06.2006"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00318606"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(90)90091-H"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-015-0724-2"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06884-x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901670103"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(00)00065-4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901390407"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20898"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi1024"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.07.019"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf1226"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07234-1"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add7046"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7721"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00760-3"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.08.021"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado3927"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.05.013"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.03.010"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141587"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90247-B"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109208"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00675-z"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.14.3089"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2013.00122"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90414-6"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac746"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1158-7"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4038"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03775-x"},{"key":"e_1_3_4_54_2","unstructured":"A. W. Erickson Cerebellar VZ derivatives. GitHub. https:\/\/github.com\/anderswe\/vz_derivatives. Deposited 22 January 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2415425122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T13:45:58Z","timestamp":1744983958000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2415425122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":54,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2025,4,29]]}},"alternative-id":["10.1073\/pnas.2415425122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2415425122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,18]]},"assertion":[{"value":"2024-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2415425122"}}