{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:11:36Z","timestamp":1787065896928,"version":"build-2736575974"},"posted":{"date-parts":[[2025,7,31]]},"group-title":"Neuroscience","reference-count":105,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/035k1ke91","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20GM103499, SC INBRE DRP to KW"],"award-info":[{"award-number":["P20GM103499, SC INBRE DRP to KW"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-NS089633 to JLT"],"award-info":[{"award-number":["R01-NS089633 to JLT"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Office of the Vice President for Research at the University of South Carolina"},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Down syndrome (DS) results from the triplication of human chromosome 21 (HSA21) and is the leading cause of intellectual disability. Down syndrome cell adhesion molecule (\n                  <jats:italic>DSCAM<\/jats:italic>\n                  ) is located on HSA21 and is overproduced in DS. DSCAM is a receptor for netrin-1 and important for neural wiring in the developing brain. Using a\n                  <jats:italic>Dscam<\/jats:italic>\n                  gain-of-function mouse model and human induced pluripotent stem cell (hiPSC)-derived cortical neurons, in combination with cellular, molecular, and behavioral approaches, this study aims to understand how\n                  <jats:italic>DSCAM<\/jats:italic>\n                  triplication and its subsequent excessive production contribute to changes in neural development and intellectual disability in DS. Analysis of morphological parameters revealed impaired neuronal development and loss of netrin-1-mediated axon guidance in mouse hippocampal pyramidal neurons overexpressing DSCAM. Furthermore, DSCAM overexpression reduces interhemispheric connectivity\n                  <jats:italic>in vivo<\/jats:italic>\n                  , and hippocampal- dependent learning in adult mice. DS hiPSC-derived excitatory pyramidal neurons exhibit a similar phenotype: impaired morphological development and loss of netrin-1-mediated axon guidance. Remarkably, normalization of DSCAM in DS hiPSC-derived neurons rescues many of these neuronal phenotypes, including reduced axon length and deficits in axon guidance. These results suggest that DSCAM plays an essential role in the development of neurons and neuronal networks, and its overproduction contributes to intellectual disability in DS.\n                <\/jats:p>","DOI":"10.1101\/2025.07.25.666804","type":"posted-content","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T15:50:15Z","timestamp":1753977015000},"source":"Crossref","is-referenced-by-count":2,"title":["Restoring DSCAM expression rescues neuronal morphology and axon guidance deficits in Down syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1274-6032","authenticated-orcid":false,"given":"Manasi","family":"Agrawal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-3217","authenticated-orcid":false,"given":"Nikita","family":"Kirkise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0115-0946","authenticated-orcid":false,"given":"Katelyn","family":"Rygel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-9409","authenticated-orcid":false,"given":"Pabitra K.","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly J.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Joyner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Aguilar-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trey R.","family":"Philip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parker S.","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2915-1588","authenticated-orcid":false,"given":"Juhi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7875-6682","authenticated-orcid":false,"given":"Jeffery","family":"Twiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-4202","authenticated-orcid":false,"given":"Aaron M.","family":"Jasnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6624-4719","authenticated-orcid":false,"given":"Kristy","family":"Welshhans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025080204100906000_2025.07.25.666804v1.1","doi-asserted-by":"crossref","unstructured":"de Graaf G , Buckley F , and Skotko BG . Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. Am J Med Genet A. 2015;167A(4):756-67.","DOI":"10.1002\/ajmg.a.37001"},{"key":"2025080204100906000_2025.07.25.666804v1.2","doi-asserted-by":"crossref","unstructured":"Parker SE , Mai CT , Canfield MA , Rickard R , Wang Y , Meyer RE , et al. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth defects research Part A, Clinical and molecular teratology. 2010;88(12):1008-16.","DOI":"10.1002\/bdra.20735"},{"issue":"1","key":"2025080204100906000_2025.07.25.666804v1.3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1684\/epd.2011.0415","article-title":"Epilepsy in children with Down syndrome","volume":"13","year":"2011","journal-title":"Epileptic disorders : international epilepsy journal with videotape"},{"key":"2025080204100906000_2025.07.25.666804v1.4","doi-asserted-by":"crossref","unstructured":"Dey A , Bhowmik K , Chatterjee A , Chakrabarty PB , Sinha S , and Mukhopadhyay K . Down Syndrome Related Muscle Hypotonia: Association with COL6A3 Functional SNP rs2270669. Frontiers in Genetics. 2013;4.","DOI":"10.3389\/fgene.2013.00057"},{"key":"2025080204100906000_2025.07.25.666804v1.5","first-page":"165","article-title":"Risks of leukaemia and solid tumours in individuals with Down\u2019s syndrome. Lancet (London","volume":"355","year":"2000","journal-title":"England"},{"issue":"3","key":"2025080204100906000_2025.07.25.666804v1.6","first-page":"353","article-title":"Alzheimer\u2019s Disease in Down Syndrome","volume":"1","year":"2012","journal-title":"European journal of neurodegenerative disease"},{"issue":"5","key":"2025080204100906000_2025.07.25.666804v1.7","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.1365-2788.2009.01158.x","article-title":"Down syndrome: a cardiovascular perspective","volume":"53","year":"2009","journal-title":"Journal of intellectual disability research : JIDR"},{"issue":"5","key":"2025080204100906000_2025.07.25.666804v1.8","doi-asserted-by":"crossref","first-page":"e1007383","DOI":"10.1371\/journal.pgen.1007383","article-title":"Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration","volume":"14","year":"2018","journal-title":"PLoS genetics"},{"issue":"1","key":"2025080204100906000_2025.07.25.666804v1.9","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jpeds.2014.09.005","article-title":"The prevalence of congenital hearing loss in neonates with Down syndrome","volume":"166","year":"2015","journal-title":"J Pediatr"},{"issue":"1","key":"2025080204100906000_2025.07.25.666804v1.10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3104\/reports.313","article-title":"Mental health, behaviour and intellectual abilities of people with Down syndrome","volume":"11","year":"2006","journal-title":"Down\u2019s syndrome, research and practice : the journal of the Sarah Duffen Centre"},{"key":"2025080204100906000_2025.07.25.666804v1.11","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.7.972"},{"key":"2025080204100906000_2025.07.25.666804v1.12","doi-asserted-by":"crossref","unstructured":"Rachidi M , and Lopes C. In: Clelland JD ed. Genomics, Proteomics, and the Nervous System. New York, NY: Springer New York; 2011:21-86.","DOI":"10.1007\/978-1-4419-7197-5_2"},{"issue":"3","key":"2025080204100906000_2025.07.25.666804v1.13","first-page":"227","article-title":"The hippocampus in Down\u2019s syndrome","volume":"27","year":"1983","journal-title":"Journal of mental deficiency research"},{"key":"2025080204100906000_2025.07.25.666804v1.14","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.10.1870"},{"key":"2025080204100906000_2025.07.25.666804v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370755"},{"key":"2025080204100906000_2025.07.25.666804v1.16","doi-asserted-by":"crossref","unstructured":"Patkee PA , Baburamani AA , Kyriakopoulou V , Davidson A , Avini E , Dimitrova R , et al. Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment. NeuroImage: Clinical. 2020;25:102139.","DOI":"10.1016\/j.nicl.2019.102139"},{"key":"2025080204100906000_2025.07.25.666804v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3314"},{"issue":"4","key":"2025080204100906000_2025.07.25.666804v1.18","first-page":"181","article-title":"Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months","volume":"9","year":"1990","journal-title":"Clin Neuropathol"},{"key":"2025080204100906000_2025.07.25.666804v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20308"},{"key":"2025080204100906000_2025.07.25.666804v1.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00113.x"},{"issue":"5","key":"2025080204100906000_2025.07.25.666804v1.21","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.aanat.2008.05.007","article-title":"Reduced cell number in the neocortical part of the human fetal brain in Down syndrome","volume":"190","year":"2008","journal-title":"Annals of Anatomy - Anatomischer Anzeiger"},{"key":"2025080204100906000_2025.07.25.666804v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.01.003"},{"key":"2025080204100906000_2025.07.25.666804v1.23","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S0140-6736(02)07497-4","article-title":"Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down\u2019s syndrome: a gene expression study","volume":"359","year":"2002","journal-title":"The Lancet"},{"key":"2025080204100906000_2025.07.25.666804v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm322"},{"key":"2025080204100906000_2025.07.25.666804v1.25","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neubiorev.2019.01.001","article-title":"Down syndrome: Neurobiological alterations and therapeutic targets","volume":"98","year":"2019","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"2025080204100906000_2025.07.25.666804v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201302848"},{"key":"2025080204100906000_2025.07.25.666804v1.27","doi-asserted-by":"crossref","unstructured":"Jain S , Watts CA , Chung WCJ , and Welshhans K . Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome. Neurosci Lett. 2020;714:134569.","DOI":"10.1016\/j.neulet.2019.134569"},{"issue":"1","key":"2025080204100906000_2025.07.25.666804v1.28","first-page":"19","article-title":"The anterior commissure in Down\u2019s syndrome","volume":"30","year":"1986","journal-title":"Journal of mental deficiency research"},{"key":"2025080204100906000_2025.07.25.666804v1.29","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530280101029"},{"key":"2025080204100906000_2025.07.25.666804v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.227"},{"key":"2025080204100906000_2025.07.25.666804v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00108-X"},{"key":"2025080204100906000_2025.07.25.666804v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1226"},{"key":"2025080204100906000_2025.07.25.666804v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00307-8"},{"key":"2025080204100906000_2025.07.25.666804v1.34","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4420"},{"key":"2025080204100906000_2025.07.25.666804v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.08.004"},{"key":"2025080204100906000_2025.07.25.666804v1.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811083106"},{"key":"2025080204100906000_2025.07.25.666804v1.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2006.00962.x"},{"key":"2025080204100906000_2025.07.25.666804v1.38","doi-asserted-by":"crossref","unstructured":"Zhang L , Huang Y , Chen JY , Ding YQ , and Song NN . DSCAM and DSCAML1 regulate the radial migration and callosal projection in developing cerebral cortex. Brain Res. 2015;1594:61\u201370.","DOI":"10.1016\/j.brainres.2014.10.060"},{"key":"2025080204100906000_2025.07.25.666804v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.030"},{"key":"2025080204100906000_2025.07.25.666804v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000230"},{"key":"2025080204100906000_2025.07.25.666804v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3396"},{"key":"2025080204100906000_2025.07.25.666804v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22360"},{"key":"2025080204100906000_2025.07.25.666804v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.020"},{"issue":"4","key":"2025080204100906000_2025.07.25.666804v1.44","doi-asserted-by":"crossref","first-page":"e3002078","DOI":"10.1371\/journal.pbio.3002078","article-title":"DSCAM gene triplication causes excessive GABAergic synapses in the neocortex in Down syndrome mouse models","volume":"21","year":"2023","journal-title":"PLoS Biol"},{"issue":"1","key":"2025080204100906000_2025.07.25.666804v1.45","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13064-018-0118-5","article-title":"DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring","volume":"13","year":"2018","journal-title":"Neural Dev"},{"key":"2025080204100906000_2025.07.25.666804v1.46","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-016-9613-9"},{"key":"2025080204100906000_2025.07.25.666804v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.11.013"},{"key":"2025080204100906000_2025.07.25.666804v1.48","doi-asserted-by":"crossref","unstructured":"Mitsogiannis MD , Pancho A , Aerts T , Sachse SM , Vanlaer R , Noterdaeme L , et al. Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration. Front Cell Dev Biol. 2020;8:624181.","DOI":"10.3389\/fcell.2020.624181"},{"key":"2025080204100906000_2025.07.25.666804v1.49","doi-asserted-by":"crossref","unstructured":"Tang XY , Xu L , Wang J , Hong Y , Wang Y , Zhu Q , et al. DSCAM\/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. J Clin Invest. 2021;131(12).","DOI":"10.1172\/JCI135763"},{"issue":"4","key":"2025080204100906000_2025.07.25.666804v1.50","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.stemcr.2018.02.001","article-title":"Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons","volume":"10","year":"2018","journal-title":"Stem cell reports"},{"key":"2025080204100906000_2025.07.25.666804v1.51","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.16-0128"},{"key":"2025080204100906000_2025.07.25.666804v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.116"},{"issue":"4","key":"2025080204100906000_2025.07.25.666804v1.53","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.stemcr.2018.08.013","article-title":"Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study","volume":"11","year":"2018","journal-title":"Stem cell reports"},{"key":"2025080204100906000_2025.07.25.666804v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.022"},{"key":"2025080204100906000_2025.07.25.666804v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/nn1775"},{"key":"2025080204100906000_2025.07.25.666804v1.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0166-11.2011"},{"key":"2025080204100906000_2025.07.25.666804v1.57","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22061"},{"key":"2025080204100906000_2025.07.25.666804v1.58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3457-10.2010"},{"key":"2025080204100906000_2025.07.25.666804v1.59","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2202-14.2015"},{"key":"2025080204100906000_2025.07.25.666804v1.60","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002"},{"key":"2025080204100906000_2025.07.25.666804v1.61","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201510107"},{"key":"2025080204100906000_2025.07.25.666804v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.08.002"},{"key":"2025080204100906000_2025.07.25.666804v1.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3406-07.2007"},{"key":"2025080204100906000_2025.07.25.666804v1.64","doi-asserted-by":"crossref","unstructured":"Rastogi M , Bartolucci M , Nanni M , Aloisio M , Vozzi D , Petretto A , et al. Integrative multi-omic analysis reveals conserved cell-projection deficits in human Down syndrome brains. Neuron. 2024.","DOI":"10.1016\/j.neuron.2024.05.002"},{"key":"2025080204100906000_2025.07.25.666804v1.65","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-232686"},{"key":"2025080204100906000_2025.07.25.666804v1.66","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200413"},{"key":"2025080204100906000_2025.07.25.666804v1.67","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294247"},{"key":"2025080204100906000_2025.07.25.666804v1.68","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688755"},{"key":"2025080204100906000_2025.07.25.666804v1.69","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)90314-0"},{"issue":"3","key":"2025080204100906000_2025.07.25.666804v1.70","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2788.1994.tb00394.x","article-title":"Dendritic and histochemical development and ageing in patients with Down\u2019s syndrome","volume":"38","year":"1994","journal-title":"Journal of intellectual disability research : JIDR"},{"key":"2025080204100906000_2025.07.25.666804v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.08.001"},{"key":"2025080204100906000_2025.07.25.666804v1.72","doi-asserted-by":"crossref","unstructured":"Chiotto AMA , Migliorero M , Pallavicini G , Bianchi FT , Gai M , Di Cunto F , et al. Neuronal Cell-Intrinsic Defects in Mouse Models of Down Syndrome. Front Neurosci. 2019;13:1081.","DOI":"10.3389\/fnins.2019.01081"},{"key":"2025080204100906000_2025.07.25.666804v1.73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.340174"},{"key":"2025080204100906000_2025.07.25.666804v1.74","doi-asserted-by":"crossref","unstructured":"Xu L , Huo HQ , Lu KQ , Tang XY , Hong Y , Han X , et al. Abnormal mitochondria in Down syndrome iPSC-derived GABAergic interneurons and organoids. Biochim Biophys Acta Mol Basis Dis. 2022:166388.","DOI":"10.1016\/j.bbadis.2022.166388"},{"key":"2025080204100906000_2025.07.25.666804v1.75","doi-asserted-by":"crossref","unstructured":"Barraza-Nunez N , Perez-Nunez R , Gaete-Ramirez B , Barrios-Garrido A , Arriagada C , Poksay K , et al. Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome. Neurotox Res. 2023.","DOI":"10.1007\/s12640-023-00638-3"},{"key":"2025080204100906000_2025.07.25.666804v1.76","doi-asserted-by":"crossref","unstructured":"Sachse SM , Lievens S , Ribeiro LF , Dascenco D , Masschaele D , Horre K , et al. Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. EMBO J. 2019.","DOI":"10.15252\/embj.201899669"},{"key":"2025080204100906000_2025.07.25.666804v1.77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052652"},{"key":"2025080204100906000_2025.07.25.666804v1.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.01.028"},{"issue":"6","key":"2025080204100906000_2025.07.25.666804v1.79","doi-asserted-by":"crossref","first-page":"e6049","DOI":"10.1590\/1414-431x20176049","article-title":"Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid precursor protein transgenic mice","volume":"50","year":"2017","journal-title":"Braz J Med Biol Res"},{"key":"2025080204100906000_2025.07.25.666804v1.80","doi-asserted-by":"crossref","unstructured":"Pizzano S , Sterne GR , Veling MW , Xu LA , Hergenreder T , and Ye B . The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes. Dis Model Mech. 2023;16(9).","DOI":"10.1242\/dmm.049725"},{"key":"2025080204100906000_2025.07.25.666804v1.81","doi-asserted-by":"crossref","unstructured":"Guo L , Wu Y , Chang H , Zhang Z , Tang H , Yu Y , et al. Structure of cell-cell adhesion mediated by the Down syndrome cell adhesion molecule. Proc Natl Acad Sci U S A. 2021;118(39).","DOI":"10.1073\/pnas.2022442118"},{"key":"2025080204100906000_2025.07.25.666804v1.82","doi-asserted-by":"crossref","unstructured":"Garrett AM , Khalil A , Walton DO , and Burgess RW . DSCAM promotes self- avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proceedings of the National Academy of Sciences. 2018.","DOI":"10.1073\/pnas.1809430115"},{"key":"2025080204100906000_2025.07.25.666804v1.83","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2525-09.2009"},{"key":"2025080204100906000_2025.07.25.666804v1.84","doi-asserted-by":"crossref","unstructured":"Pennington BF , Moon J , Edgin J , Stedron J , and Nadel L. The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev. 2003;74(1):75- 93.","DOI":"10.1111\/1467-8624.00522"},{"issue":"3","key":"2025080204100906000_2025.07.25.666804v1.85","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/wcs.1221","article-title":"Cognition in Down syndrome: a developmental cognitive neuroscience perspective","volume":"4","year":"2013","journal-title":"Wiley Interdiscip Rev Cogn Sci"},{"key":"2025080204100906000_2025.07.25.666804v1.86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021879"},{"issue":"6","key":"2025080204100906000_2025.07.25.666804v1.87","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/j.1365-2214.2011.01306.x","article-title":"Behavioural profile and maternal stress in Greek young children with Williams syndrome","volume":"38","year":"2012","journal-title":"Child Care Health Dev"},{"key":"2025080204100906000_2025.07.25.666804v1.88","doi-asserted-by":"crossref","unstructured":"Edwards G , Jones C , Pearson E , Royston R , Oliver C , Tarver J , et al. Prevalence of anxiety symptomatology and diagnosis in syndromic intellectual disability: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022;138:104719.","DOI":"10.1016\/j.neubiorev.2022.104719"},{"key":"2025080204100906000_2025.07.25.666804v1.89","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2202-14.2015"},{"key":"2025080204100906000_2025.07.25.666804v1.90","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002"},{"key":"2025080204100906000_2025.07.25.666804v1.91","doi-asserted-by":"crossref","unstructured":"Jain S , Watts CA , Chung WCJ , and Welshhans K . Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome. Neurosci Lett. 2020;714:134569.","DOI":"10.1016\/j.neulet.2019.134569"},{"key":"2025080204100906000_2025.07.25.666804v1.92","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22360"},{"issue":"5","key":"2025080204100906000_2025.07.25.666804v1.93","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1038\/nprot.2006.356","article-title":"Culturing hippocampal neurons","volume":"1","year":"2006","journal-title":"Nature Protocols"},{"key":"2025080204100906000_2025.07.25.666804v1.94","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0166-11.2011"},{"key":"2025080204100906000_2025.07.25.666804v1.95","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.16-0128"},{"key":"2025080204100906000_2025.07.25.666804v1.96","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.116"},{"issue":"4","key":"2025080204100906000_2025.07.25.666804v1.97","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.stemcr.2018.08.013","article-title":"Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study","volume":"11","year":"2018","journal-title":"Stem cell reports"},{"key":"2025080204100906000_2025.07.25.666804v1.98","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201510107"},{"key":"2025080204100906000_2025.07.25.666804v1.99","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.022"},{"key":"2025080204100906000_2025.07.25.666804v1.100","doi-asserted-by":"crossref","unstructured":"Harb K , Bertacchi M , and Studer M . Optimized Immunostaining of Embryonic and Early Postnatal Mouse Brain Sections. Bio-protocol. 2021:e3868.","DOI":"10.21769\/BioProtoc.3868"},{"key":"2025080204100906000_2025.07.25.666804v1.101","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22061"},{"key":"2025080204100906000_2025.07.25.666804v1.102","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2411811122"},{"key":"2025080204100906000_2025.07.25.666804v1.103","doi-asserted-by":"crossref","unstructured":"Boyer NP , Monkiewicz C , Menon S , Moy SS , and Gupton SL . Mammalian TRIM67 Functions in Brain Development and Behavior. eNeuro. 2018;5(3).","DOI":"10.1523\/ENEURO.0186-18.2018"},{"key":"2025080204100906000_2025.07.25.666804v1.104","doi-asserted-by":"crossref","unstructured":"Dutta S , Beaver J , Halcomb CJ , and Jasnow AM . Dissociable roles of the nucleus accumbens core and shell subregions in the expression and extinction of conditioned fear. Neurobiol Stress. 2021;15:100365.","DOI":"10.1016\/j.ynstr.2021.100365"},{"key":"2025080204100906000_2025.07.25.666804v1.105","doi-asserted-by":"publisher","DOI":"10.1101\/lm.032961.113"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.25.666804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:14:27Z","timestamp":1768468467000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.25.666804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":105,"URL":"https:\/\/doi.org\/10.1101\/2025.07.25.666804","relation":{},"subject":[],"published":{"date-parts":[[2025,7,31]]},"subtype":"preprint"}}