{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:18:49Z","timestamp":1783491529336,"version":"3.55.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015504","name":"Simons Initiative for the Developing Brain","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015504","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>\n                    The 574-kilobase pair\n                    <jats:italic>16p11.2<\/jats:italic>\n                    microdeletion raises a person\u2019s odds for neurodevelopmental and energy balance conditions, particularly autism and obesity, with considerable clinical heterogeneity, and how much this reflects genetic versus environmental or stochastic factors is unclear. GABAergic forebrain interneurons originate from progenitors residing in the ventricular zones of the fetal ventral telencephalon, and their perturbation is implicated in\n                    <jats:italic>16p11.2<\/jats:italic>\n                    phenotypes, prompting investigation of how the\n                    <jats:italic>16p11.2<\/jats:italic>\n                    microdeletion impacts their development. Here we studied human-induced pluripotent stem cell (IPSC) derived ventral telencephalic interneuron progenitors in two-dimensional culture, comparing IPSCs isogenic except for a heterozygous\n                    <jats:italic>16p11.2<\/jats:italic>\n                    microdeletion to minimize confounding effects of genetic background. Single-cell RNA sequencing generated single-cell transcriptome populations for comparative bioinformatics, revealing hundreds of differentially expressed transcripts, many associated with cell signaling, chromatin biology, and neurodevelopmental conditions. Pertinently, we find that transcript level variation is significantly greater between\n                    <jats:italic>16p11.2<\/jats:italic>\n                    heterozygous progenitors than their isogenic wild type counterparts both for sets of genes comprising regulons, gene-sets functionally connected by transcription factor regulation, and for randomly selected gene sets. This indicates that the\n                    <jats:italic>16p11.2<\/jats:italic>\n                    locus itself has a genome-wide property in stabilizing transcription between cells. Regulons with the greatest increased variability in\n                    <jats:italic>16p11.2<\/jats:italic>\n                    heterozygous progenitors exhibit strong enrichment for cell cycle-related genes, and many are regulated by transcription factors themselves associated with autism and\/or obesity, suggesting the hypothesis that enhanced transcriptional variation contributes to\n                    <jats:italic>16p11.2<\/jats:italic>\n                    microdeletion phenotypes.\n                  <\/jats:p>","DOI":"10.3389\/fnmol.2026.1872405","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:57:29Z","timestamp":1783490249000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["16p11.2 microdeletion enhances gene expression variability between human IPSC-derived forebrain interneuron progenitor cells in culture"],"prefix":"10.3389","volume":"19","author":[{"given":"Yifei","family":"Yang","sequence":"first","affiliation":[{"name":"Simons Initiative for the Developing Brain, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Edinburgh Medical School Biomedical Sciences, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idoia","family":"Quintana Urzainqui","sequence":"additional","affiliation":[{"name":"Simons Initiative for the Developing Brain, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Developmental Biology Unit, European Molecular Biology Laboratory (EMBL)","place":["Heidelberg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pratt","sequence":"additional","affiliation":[{"name":"Simons Initiative for the Developing Brain, University of Edinburgh","place":["Edinburgh, United Kingdom"]},{"name":"Edinburgh Medical School Biomedical Sciences, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref1","first-page":"2074","volume-title":"Mol Vis","author":"Abouzeid","year":"2009"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.abf8683","article-title":"Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity","volume":"373","author":"Akbari","year":"2021","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.neuron.2018.12.026","article-title":"Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models","volume":"101","author":"Antoine","year":"2019","journal-title":"Neuron"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e1005709","DOI":"10.1371\/journal.pgen.1005709","article-title":"Reciprocal effects on neurocognitive and metabolic phenotypes in mouse models of 16p11.2 deletion and duplication syndromes","volume":"12","author":"Arbogast","year":"2016","journal-title":"PLoS Genet."},{"key":"ref6","first-page":"463","article-title":"Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital Aniridia due to PAX6 mutations","volume-title":"Arch Pediatr Adolesc Med","author":"Bamiou","year":"2007"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1242\/dmm.009944","article-title":"Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes","volume":"5","author":"Blaker-Lee","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.ajhg.2014.05.004","article-title":"Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex and multiplex autism families","volume":"94","author":"Blumenthal","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1111\/ejn.13595","article-title":"Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation\/inhibition imbalance","volume":"47","author":"Bozzi","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00018-024-05129-y","article-title":"RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1","volume":"81","author":"Choi","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e1009484","DOI":"10.1371\/journal.pcbi.1009484","article-title":"Experiment level curation of transcriptional regulatory interactions in neurodevelopment","volume":"17","author":"Chu","year":"2021","journal-title":"PLoS Comput. Biol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.gde.2021.01.011","article-title":"16p11.2 deletion syndrome","volume":"68","author":"Chung","year":"2021","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fgene.2022.818574","article-title":"Calculating polygenic risk scores (PRS) in UK Biobank: a practical Guide for epidemiologists","volume":"13","author":"Collister","year":"2022","journal-title":"Front. Genet."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.stemcr.2022.04.019","article-title":"Autism NPCs from both idiopathic and CNV 16p11.2 deletion patients exhibit dysregulation of proliferation and mitogenic responses","volume":"17","author":"Connacher","year":"2022","journal-title":"Stem Cell Reports"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1001\/jamapsychiatry.2015.2123","article-title":"Defining the effect of the 16p11.2 duplication on cognition, behavior, and medical comorbidities","volume":"73","author":"D\u2019Angelo","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"5102","DOI":"10.1158\/0008-5472.CAN-18-3882","article-title":"Differential variation analysis enables detection of tumor heterogeneity using single-cell RNA-sequencing data","volume":"79","author":"Davis-Marcisak","year":"2019","journal-title":"Cancer Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/nn.3141","article-title":"Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex","volume":"15","author":"de Anda","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00311","article-title":"E2F1, a novel regulator of metabolism","volume":"8","author":"Denechaud","year":"2017","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1016\/j.celrep.2017.11.037","article-title":"Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism Spectrum disorder","volume":"21","author":"Deshpande","year":"2017","journal-title":"Cell Rep."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.ajhg.2019.07.020","article-title":"Germline 16p11.2 microdeletion predisposes to neuroblastoma","volume":"105","author":"Egolf","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature24470","article-title":"Kctd13 deletion reduces synaptic transmission via increased RhoA","volume":"551","author":"Escamilla","year":"2017","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1038\/ijo.2013.11","article-title":"Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions","volume":"37","author":"Fern\u00e1ndez-Real","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201227","article-title":"16p11.2 deletion accelerates subpallial maturation and increases variability in human iPSC-derived ventral telencephalic organoids","volume":"150","author":"Fetit","year":"2023","journal-title":"Development"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/YPG.0000000000000259","article-title":"Understanding the clinical manifestations of 16p11.2 deletion syndrome: a series of developmental case reports in children","volume":"30","author":"Fetit","year":"2020","journal-title":"Psychiatr. Genet."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13229-019-0262-8","article-title":"Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer","volume":"10","author":"For\u00e9s-Martos","year":"2019","journal-title":"Mol. Autism."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1056\/NEJMoa1200395","article-title":"Phenotypic heterogeneity of genomic disorders and rare copy-number variants","volume":"367","author":"Girirajan","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nature11091","article-title":"KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant","volume":"485","author":"Golzio","year":"2012","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"147283","DOI":"10.1016\/j.brainres.2021.147283","article-title":"Structural and functional consequences of PAX6 mutations in the brain: implications for aniridia","volume":"1756","author":"Grant","year":"2021","journal-title":"Brain Res."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1080\/15548627.2015.1094597","article-title":"Elevated autophagy gene expression in adipose tissue of obese humans: a potential non-cell-cycle-dependent function of E2F1","volume":"11","author":"Haim","year":"2015","journal-title":"Autophagy"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/jsr.12345","article-title":"Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency","volume":"25","author":"Hanish","year":"2016","journal-title":"J. Sleep Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1038\/nn.3541","article-title":"Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences","volume":"16","author":"Hansen","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1038\/s41436-021-01114-z","article-title":"Disruption of RFX family transcription factors causes autism, attention-deficit\/hyperactivity disorder, intellectual disability, and dysregulated behavior","volume":"23","author":"Harris","year":"2021","journal-title":"Genet. Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"17076","DOI":"10.1073\/pnas.1114042108","article-title":"Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism","volume":"108","author":"Horev","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1002\/aur.2332","article-title":"Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers","volume":"13","author":"Hudac","year":"2020","journal-title":"Autism Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nature10406","article-title":"Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus","volume":"478","author":"Jacquemont","year":"2011","journal-title":"Nature"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1002\/aur.1838","article-title":"Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients","volume":"10","author":"Kalikiri","year":"2017","journal-title":"Autism Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1007\/s12035-019-01727-1","article-title":"CRISPR\/Cas9-mediated knockout of the neuropsychiatric risk gene KCTD13 causes developmental deficits in human cortical neurons derived from induced pluripotent stem cells","volume":"57","author":"Kizner","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.neuron.2018.10.009","article-title":"Development and functional diversification of cortical interneurons","volume":"100","author":"Lim","year":"2018","journal-title":"Neuron"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1038\/nprot.2013.106","article-title":"Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells","volume":"8","author":"Liu","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/emboj.2013.25","article-title":"PRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location","volume":"32","author":"Lu","year":"2013","journal-title":"EMBO J."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1038\/nn.3536","article-title":"Subcortical origins of human and monkey neocortical interneurons","volume":"16","author":"Ma","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.neulet.2009.07.021","article-title":"A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient","volume":"462","author":"Maekawa","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/ijo.2015.247","article-title":"16p11.2 locus modulates response to satiety before the onset of obesity","volume":"40","author":"Maillard","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3389\/fncel.2015.00070","article-title":"Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor","volume":"9","author":"Manuel","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e70136","DOI":"10.1111\/ejn.70136","article-title":"Development of GABAergic interneurons in the human cerebral cortex","volume":"61","author":"Marin","year":"2025","journal-title":"Eur. J. Neurosci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.ajhg.2015.04.002","article-title":"A potential contributory role for ciliary dysfunction in the 16p11.2 600 kb BP4-BP5 pathology","volume":"96","author":"Migliavacca","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"4038","DOI":"10.1093\/cercor\/bhab067","article-title":"Expression of genes in the 16p11.2 locus during development of the human fetal cerebral cortex","volume":"31","author":"Morson","year":"2021","journal-title":"Cereb. Cortex"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.neuron.2015.07.033","article-title":"Excitatory\/inhibitory balance and circuit homeostasis in autism Spectrum disorders","volume":"87","author":"Nelson","year":"2015","journal-title":"Neuron"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0441-6","article-title":"Psychiatric disorders in children with 16p11.2 deletion and duplication","volume":"9","author":"Niarchou","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nature19075","article-title":"Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility","volume":"536","author":"Nuttle","year":"2016","journal-title":"Nature"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"8663","DOI":"10.1523\/JNEUROSCI.1107-12.2012","article-title":"Disrupted ERK signaling during cortical development leads to abnormal progenitor proliferation, neuronal and network excitability and behavior, modeling human neuro-cardio-facial-cutaneous and related syndromes","volume":"32","author":"Pucilowska","year":"2012","journal-title":"J. Neurosci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1523\/JNEUROSCI.0515-17.2018","article-title":"Pharmacological inhibition of ERK signaling rescues pathophysiology and behavioral phenotype associated with 16p11.2 chromosomal deletion in mice","volume":"38","author":"Pucilowska","year":"2018","journal-title":"J. Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.1523\/JNEUROSCI.4864-13.2015","article-title":"The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway","volume":"35","author":"Pucilowska","year":"2015","journal-title":"J. Neurosci."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1002\/aur.1691","article-title":"Reduced GABA and altered somatosensory function in children with autism spectrum disorder","volume":"10","author":"Puts","year":"2017","journal-title":"Autism Res."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1016\/j.celrep.2019.08.071","article-title":"Oligogenic effects of 16p11.2 copy-number variation on craniofacial development","volume":"28","author":"Qiu","year":"2019","journal-title":"Cell Rep."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"11199","DOI":"10.1523\/JNEUROSCI.1366-14.2014","article-title":"Opposing brain differences in 16p11.2 deletion and duplication carriers","volume":"34","author":"Qureshi","year":"2014","journal-title":"J. Neurosci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.tins.2017.05.004","article-title":"The role of interneurons in autism and Tourette syndrome","volume":"40","author":"Rapanelli","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/j.tins.2020.09.001","article-title":"16p11.2 copy number variations and neurodevelopmental disorders","volume":"43","author":"Rein","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1038\/s41380-018-0025-5","article-title":"Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling","volume":"24","author":"Richter","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.cub.2015.11.019","article-title":"Reduced GABAergic action in the autistic brain","volume":"26","author":"Robertson","year":"2016","journal-title":"Curr. Biol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1038\/s41591-023-02408-2","article-title":"Phenotypic effects of genetic variants associated with autism","volume":"29","author":"Rolland","year":"2023","journal-title":"Nat. Med."},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58178","article-title":"16p11.2 microdeletion imparts transcriptional alterations in human iPSC-derived models of early neural development","volume":"9","author":"Roth","year":"2020","journal-title":"eLife"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1034\/j.1601-183X.2003.00037.x","article-title":"Model of autism: increased ratio of excitation\/inhibition in key neural systems","volume":"2","author":"Rubenstein","year":"2003","journal-title":"Genes Brain Behav."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.ajhg.2023.04.010","article-title":"Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene\u2019s candidacy in 6q16.1 deletions","volume":"110","author":"Sch\u00f6nauer","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1056\/NEJMra1010172","article-title":"Mechanisms of disease ciliopathies","volume":"364","author":"Schwartz","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"eabj6641","DOI":"10.1126\/science.abj6641","article-title":"Mouse and human share conserved transcriptional programs for interneuron development","volume":"374","author":"Shi","year":"2021","journal-title":"Science"},{"key":"ref68","first-page":"15545","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume-title":"Proc Natl Acad Sci U S A","author":"Subramanian","year":"2005"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1038\/s41467-021-23113-z","article-title":"16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro","volume":"12","author":"Sundberg","year":"2021","journal-title":"Nat. Commun."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nn.4235","article-title":"Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR","volume":"19","author":"Tai","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.ajhg.2025.02.011","article-title":"Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions","volume":"112","author":"Upadhya","year":"2025","journal-title":"Am. J. Hum. Genet."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"7560","DOI":"10.1038\/s41380-021-01243-6","article-title":"Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism","volume":"26","author":"Urresti","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nature08727","article-title":"A new highly penetrant form of obesity due to deletions on chromosome 16p11.2","volume":"463","author":"Walters","year":"2010","journal-title":"Nature"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13229-017-0124-1","article-title":"CRISPR\/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells","volume":"8","author":"Wang","year":"2017","journal-title":"Mol. Autism."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1056\/NEJMoa075974","article-title":"Association between microdeletion and microduplication at 16p11.2 and autism","volume":"358","author":"Weiss","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.neuron.2016.12.006","article-title":"TAOK2 kinase mediates PSD95 stability and dendritic spine maturation through Septin7 phosphorylation","volume":"93","author":"Yadav","year":"2017","journal-title":"Neuron"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12868-022-00771-3","article-title":"Identifying foetal forebrain interneurons as a target for monogenic autism risk factors and the polygenic 16p11.2 microdeletion","volume":"24","author":"Yang","year":"2023","journal-title":"BMC Neurosci."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/acn3.297","article-title":"PAX6, brain structure and function in human adults: advanced MRI in aniridia","volume":"3","author":"Yogarajah","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1038\/s41593-021-00940-3","article-title":"Interneuron origin and molecular diversity in the human fetal brain","volume":"24","author":"Yu","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nm.3792","article-title":"Whole-genome sequencing of quartet families with autism spectrum disorder","volume":"21","author":"Yuen","year":"2015","journal-title":"Nat. Med."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"107521","DOI":"10.1016\/j.celrep.2020.03.085","article-title":"Imbalance of excitatory\/inhibitory neuron differentiation in neurodevelopmental disorders with an NR2F1 point mutation","volume":"31","author":"Zhang","year":"2020","journal-title":"Cell Rep."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"149554","DOI":"10.1016\/j.gene.2025.149554","article-title":"Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone receptor","volume":"962","author":"Zhu","year":"2025","journal-title":"Gene"}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2026.1872405\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:57:32Z","timestamp":1783490252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2026.1872405\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":84,"alternative-id":["10.3389\/fnmol.2026.1872405"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2026.1872405","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1872405"}}