{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:11:59Z","timestamp":1791241919004,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canada First Research Excellence Fund"},{"name":"Healthy Brains, Healthy Lives initiative at McGill University"},{"name":"Alain and Sandra Bouchard Foundation"},{"name":"Chamandy Foundation"},{"name":"Djavad Mowafaghian Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fragile X syndrome (FXS) is caused by a repression of the FMR1 gene that codes the Fragile X mental retardation protein (FMRP), an RNA binding protein involved in processes that are crucial for proper brain development. To better understand the consequences of the absence of FMRP, we analyzed gene expression profiles and activities of cortical neural progenitor cells (NPCs) and neurons obtained from FXS patients\u2019 induced pluripotent stem cells (IPSCs) and IPSC-derived cells from FMR1 knock-out engineered using CRISPR-CAS9 technology. Multielectrode array recordings revealed in FMR1 KO and FXS patient cells, decreased mean firing rates; activities blocked by tetrodotoxin application. Increased expression of presynaptic mRNA and transcription factors involved in the forebrain specification and decreased levels of mRNA coding AMPA and NMDA subunits were observed using RNA sequencing on FMR1 KO neurons and validated using quantitative PCR in both models. Intriguingly, 40% of the differentially expressed genes were commonly deregulated between NPCs and differentiating neurons with significant enrichments in FMRP targets and autism-related genes found amongst downregulated genes. Our findings suggest that the absence of FMRP affects transcriptional profiles since the NPC stage, and leads to impaired activity and neuronal differentiation over time, which illustrates the critical role of FMRP protein in neuronal development.<\/jats:p>","DOI":"10.3390\/ijms241914926","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T01:07:13Z","timestamp":1696554433000},"page":"14926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transcriptional Dysregulation and Impaired Neuronal Activity in FMR1 Knock-Out and Fragile X Patients\u2019 iPSC-Derived Models"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-6238","authenticated-orcid":false,"given":"Gilles","family":"Maussion","sequence":"first","affiliation":[{"name":"The Neuro\u2019s Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Rocha","sequence":"additional","affiliation":[{"name":"The Neuro\u2019s Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges","family":"Abdian","sequence":"additional","affiliation":[{"name":"The Neuro\u2019s Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Yang","sequence":"additional","affiliation":[{"name":"The Neuro\u2019s Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Turk","sequence":"additional","affiliation":[{"name":"The Neuro\u2019s Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, 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