{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:59:07Z","timestamp":1785491947557,"version":"3.56.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The Epidermal Growth Factor Receptor (EGFR) is a key regulator of neurodevelopment, controlling the proliferation, differentiation, and self\u2010renewal of neural stem and progenitor cells. Dysregulated EGFR signaling has been implicated in schizophrenia, a neurodevelopmental disorder associated with abnormal cortical maturation. We investigated EGFR\u2010dependent signaling in neural stem\/progenitor cells derived from olfactory neuroepithelium (hereafter referred to as Olfactory Neural Stem\/Progenitor Cells, ONSPCs) collected from individuals with no prior history of psychiatric disorders (hereafter referred to as healthy controls, HC) and patients diagnosed with schizophrenia (schizophrenic, SZ), an ex vivo human model that retains disease\u2010related molecular signatures. Both HC\u2010 and SZ\u2010derived ONSPCs formed neurospheres under proliferative conditions in the presence of the growth factors Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF), confirming their neural progenitor identity. However, under EGF\u2010exclusive conditions, HC\u2010derived ONSPCs generated compact, well\u2010organized neurospheres, whereas SZ\u2010derived ONSPCs produced sparse, irregular aggregates, indicating impaired responsiveness to EGF. Despite comparable EGFR protein levels between groups, EGF stimulation revealed distinct dynamics of downstream EGFR effectors. In HC\u2010derived ONSPCs, EGFR activation was initially modest but sustained over time, whereas in SZ\u2010derived cells it was more rapid and transiently stronger, followed by early signal decay. In particular, Akt and Src, which are implicated in signaling pathways driving proliferation and self\u2010renewal, displayed activation dynamics paralleling those of EGFR in each group. These findings are consistent with dysregulation of the magnitude and temporal dynamics of EGFR\u2013dependent signaling in SZ\u2010derived ONSPCs, associated with impaired neurosphere formation under EGF\u2010exclusive conditions and suggestive of reduced self\u2010renewal capacity. Although limited by the modest sample size, the semiquantitative nature of Western blot analyses, and the potential effect of medication exposure, this study supports the relevance of patient\u2010derived ONSPCs as a physiologically meaningful platform for investigating neurodevelopmental mechanisms underlying schizophrenia.<\/jats:p>","DOI":"10.1002\/cbin.70181","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:23:31Z","timestamp":1782739411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired Neurosphere Formation as a Functional Readout of Aberrant EGFR Signaling Kinetics in Olfactory Neural Progenitors From Patients With Schizophrenia"],"prefix":"10.1002","volume":"50","author":[{"given":"Tommaso","family":"Toffanin","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-7658","authenticated-orcid":false,"given":"Mario Angelo","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Idotta","sequence":"additional","affiliation":[{"name":"Metis ETS San Martino di Lupari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Salvi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bosello\u2010Travain","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lina","family":"Massimino","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Section of Padova National Research Council (CNR) Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Saetti","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology San Bortolo Hospital Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Silvestrini","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology San Bortolo Hospital Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Meneghetti","sequence":"additional","affiliation":[{"name":"Department of Mental Health Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Mental Health Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giulia","family":"Nanni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosangela","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-1895","authenticated-orcid":false,"given":"Chiara","family":"Montemitro","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Zerbinati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino Belvederi","family":"Murri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-4494","authenticated-orcid":false,"given":"Luigi","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Brunati","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09347"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-02780-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.07.009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2014.141"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80937-X"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06301-4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01133-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00813.2024"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.10.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0920-9964(99)00055-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001081"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117677"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.246"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2019.06.004"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2024.2357096"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799859611"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291712000736"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.11.028"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.011"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020768"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.04.002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4993"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.06.019"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1220"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2005.10.012"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.29"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2020.06.003"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15009"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701184"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells6020013"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001642"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1553558"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.10.1472"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7618085"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.01.014"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-11-73"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.045"},{"key":"e_1_2_11_40_1","volume-title":"The Maudsley Prescribing Guidelines in Psychiatry","author":"Taylor D. M.","year":"2025"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000069"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41537-016-0006-0"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.042317"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600988"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9050052"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X693040"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.70181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.70181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.70181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:21:07Z","timestamp":1785489667000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.70181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/cbin.70181"],"URL":"https:\/\/doi.org\/10.1002\/cbin.70181","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"2025-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70181"}}