{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:23:47Z","timestamp":1784809427906,"version":"3.55.0"},"reference-count":160,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T00:00:00Z","timestamp":1713657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US Department of Defense Neurofibromatosis Program","award":["W81WXH-20-1-0255"],"award-info":[{"award-number":["W81WXH-20-1-0255"]}]},{"name":"US Department of Defense Neurofibromatosis Program","award":["CTF-2022-05-004"],"award-info":[{"award-number":["CTF-2022-05-004"]}]},{"name":"Children\u2019s Tumor Foundation Drug Discovery Initiative","award":["W81WXH-20-1-0255"],"award-info":[{"award-number":["W81WXH-20-1-0255"]}]},{"name":"Children\u2019s Tumor Foundation Drug Discovery Initiative","award":["CTF-2022-05-004"],"award-info":[{"award-number":["CTF-2022-05-004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurofibromatosis 1 (NF1) is a multisymptomatic disorder with highly variable presentations, which include short stature, susceptibility to formation of the characteristic benign tumors known as neurofibromas, intense freckling and skin discoloration, and cognitive deficits, which characterize most children with the condition. Attention deficits and Autism Spectrum manifestations augment the compromised learning presented by most patients, leading to behavioral problems and school failure, while fragmented sleep contributes to chronic fatigue and poor quality of life. Neurofibromin (Nf1) is present ubiquitously during human development and postnatally in most neuronal, oligodendrocyte, and Schwann cells. Evidence largely from animal models including Drosophila suggests that the symptomatic variability may reflect distinct cell-type-specific functions of the protein, which emerge upon its loss, or mutations affecting the different functional domains of the protein. This review summarizes the contributions of Drosophila in modeling multiple NF1 manifestations, addressing hypotheses regarding the cell-type-specific functions of the protein and exploring the molecular pathways affected upon loss of the highly conserved fly homolog dNf1. Collectively, work in this model not only has efficiently and expediently modelled multiple aspects of the condition and increased understanding of its behavioral manifestations, but also has led to pharmaceutical strategies towards their amelioration.<\/jats:p>","DOI":"10.3390\/cells13080721","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T09:53:52Z","timestamp":1713779632000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Drosophila Contributions towards Understanding Neurofibromatosis 1"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6101-7147","authenticated-orcid":false,"given":"Kalliopi","family":"Atsoniou","sequence":"first","affiliation":[{"name":"Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Athens, Greece"},{"name":"Laboratory of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3271-6436","authenticated-orcid":false,"given":"Eleni","family":"Giannopoulou","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-6144","authenticated-orcid":false,"given":"Eirini-Maria","family":"Georganta","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5113-6192","authenticated-orcid":false,"given":"Efthimios M. C.","family":"Skoulakis","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13023-020-1310-3","article-title":"Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966","volume":"15","author":"Bergqvist","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-5793(02)02887-9","article-title":"Quantification of NF1 transcripts reveals novel highly expressed splice variants","volume":"522","author":"Vandenbroucke","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.4161\/cc.3.10.1182","article-title":"Ras\/Raf\/ERK signalling and NF1","volume":"3","author":"Harrisingh","year":"2004","journal-title":"Cell Cycle"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8573","DOI":"10.1073\/pnas.0503224102","article-title":"The NF1 tumor suppressor critically regulates TSC2 and mTOR","volume":"102","author":"Johannessen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(90)90150-D","article-title":"The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21","volume":"63","author":"Martin","year":"1990","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nn792","article-title":"Neurofibromin regulates G protein-stimulated adenylyl cyclase activity","volume":"5","author":"Tong","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/hmg\/ddx264","article-title":"Neurofibromatosis type 1 alternative splicing is a key regulator of Ras\/ERK signaling and learning behaviors in mice","volume":"26","author":"Nguyen","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/jama.1997.03550010065042","article-title":"The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2","volume":"278","author":"Gutmann","year":"1997","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1126\/science.2134734","article-title":"Type 1 neurofibromatosis gene: Identification of a large transcript disrupted in three NF1 patients","volume":"249","author":"Wallace","year":"1990","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5873","DOI":"10.18632\/oncotarget.2194","article-title":"The NF1 gene revisited\u2014From bench to bedside","volume":"5","author":"Yap","year":"2014","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0896-6273(92)90270-N","article-title":"The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes","volume":"8","author":"Daston","year":"1992","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9658","DOI":"10.1073\/pnas.88.21.9658","article-title":"Identification of the neurofibromatosis type 1 gene product","volume":"88","author":"Gutmann","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","first-page":"1555","article-title":"Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation","volume":"6","author":"Nishi","year":"1991","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1038\/nrdp.2017.4","article-title":"Neurofibromatosis type 1","volume":"3","author":"Gutmann","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/1346-8138.13218","article-title":"Nutritional, muscular and metabolic characteristics in patients with neurofibromatosis type 1","volume":"43","author":"Koga","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Peduto, C., Zanobio, M., Nigro, V., Perrotta, S., Piluso, G., and Santoro, C. (2023). Neurofibromatosis Type 1: Pediatric Aspects and Review of Genotype-Phenotype Correlations. Cancers, 15.","DOI":"10.3390\/cancers15041217"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1590\/1806-9282.62.09.831","article-title":"Body composition in adults with neurofibromatosis type 1","volume":"62","author":"Souza","year":"2016","journal-title":"Rev. Assoc. Med. Bras. (1992)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1017\/S0012162205000460","article-title":"Psychological disturbance and sleep disorders in children with neurofibromatosis type 1","volume":"47","author":"Johnson","year":"2005","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/ajmg.a.35915","article-title":"Sleep disturbance as part of the neurofibromatosis type 1 phenotype in adults","volume":"161","author":"Leschziner","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1177\/0883073813500849","article-title":"Prevalence of Sleep Disturbances in Children with Neurofibromatosis Type 1","volume":"28","author":"Licis","year":"2013","journal-title":"J. Child Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1001\/jamapsychiatry.2016.2600","article-title":"Disease Burden and Symptom Structure of Autism in Neurofibromatosis Type 1: A Study of the International NF1-ASD Consortium Team (INFACT)","volume":"73","author":"Morris","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-neuro-060909-153215","article-title":"Molecular and Cellular Mechanisms of Learning Disabilities: A Focus on NF1","volume":"33","author":"Shilyansky","year":"2010","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fped.2017.00227","article-title":"Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1","volume":"5","year":"2017","journal-title":"Front. Pediatr."},{"key":"ref_24","first-page":"973","article-title":"Learning disabilities in children with neurofibromatosis type 1: Subtypes, cognitive profile, and attention-deficit-hyperactivity disorder","volume":"48","author":"Hyman","year":"2006","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1212\/01.WNL.0000055090.78351.C1","article-title":"Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1","volume":"60","author":"Hyman","year":"2003","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1177\/088307380201700811","article-title":"Cognitive deficits in neurofibromatosis 1","volume":"17","author":"North","year":"2002","journal-title":"J. Child Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1912735","article-title":"Selumetinib in Children with Inoperable Plexiform Neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1055\/s-0034-1368117","article-title":"Pharmacotherapy of attention deficit in neurofibromatosis type 1: Effects on cognition","volume":"45","author":"Lidzba","year":"2014","journal-title":"Neuropediatrics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s13023-014-0142-4","article-title":"The effect of methylphenidate on neurofibromatosis type 1: A randomised, double-blind, placebo-controlled, crossover trial","volume":"9","author":"Gueyffier","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1469-8749.2002.tb00780.x","article-title":"Treatment of ADHD in neurofibromatosis type 1","volume":"44","author":"Mautner","year":"2002","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bergoug, M., Doudeau, M., Godin, F., Mosrin, C., Vall\u00e9e, B., and B\u00e9n\u00e9detti, H. (2020). Neurofibromin Structure, Functions and Regulation. Cells, 9.","DOI":"10.3390\/cells9112365"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00439-017-1766-y","article-title":"Emerging genotype-phenotype relationships in patients with large NF1 deletions","volume":"136","author":"Mautner","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/humu.23929","article-title":"Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: Genotype-phenotype study in neurofibromatosis type 1","volume":"41","author":"Koczkowska","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s41436-018-0269-0","article-title":"Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): An update of genotype-phenotype correlation","volume":"21","author":"Koczkowska","year":"2019","journal-title":"Genet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ajhg.2017.12.001","article-title":"Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848","volume":"102","author":"Koczkowska","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"dmm049362","DOI":"10.1242\/dmm.049362","article-title":"RAS and beyond: The many faces of the neurofibromatosis type 1 protein","volume":"15","author":"Anastasaki","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_37","first-page":"305","article-title":"An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): Evidence for modifying genes","volume":"53","author":"Easton","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/ajmg.a.33851","article-title":"Variable expression of neurofibromatosis 1 in monozygotic twins","volume":"155","author":"Rieley","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/14728222.2018.1465931","article-title":"Emerging therapeutic targets for neurofibromatosis type 1","volume":"22","author":"Walker","year":"2018","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1038\/s41388-021-01979-z","article-title":"Tumorigenesis in neurofibromatosis type 1: Role of the microenvironment","volume":"40","author":"Jiang","year":"2021","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Osum, S.H., Watson, A.L., and Largaespada, D.A. (2021). Spontaneous and Engineered Large Animal Models of Neurofibromatosis Type 1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041954"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.molcel.2022.03.011","article-title":"Structural basis of activation of the tumor suppressor protein neurofibromin","volume":"82","author":"Werten","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/S0021-9258(17)49919-4","article-title":"Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer","volume":"295","author":"Sherekar","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e2208960120","DOI":"10.1073\/pnas.2208960120","article-title":"Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization","volume":"120","author":"Young","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.stemcr.2020.03.007","article-title":"Human iPSC-Derived Neurons and Cerebral Organoids Establish Differential Effects of Germline NF1 Gene Mutations","volume":"14","author":"Anastasaki","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/sj.neo.7900249","article-title":"Mouse models of neurofibromatosis 1 and 2","volume":"4","author":"Gutmann","year":"2002","journal-title":"Neoplasia"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Isakson, S.H., Rizzardi, A.E., Coutts, A.W., Carlson, D.F., Kirstein, M.N., Fisher, J., Vitte, J., Williams, K.B., Pluhar, G.E., and Dahiya, S. (2018). Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1. Commun. Biol., 1.","DOI":"10.1038\/s42003-018-0163-y"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"dmm049422","DOI":"10.1242\/dmm.049422","article-title":"Mechanistic insights from animal models of neurofibromatosis type 1 cognitive impairment","volume":"15","author":"Miller","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1177\/088307380201700813","article-title":"Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1","volume":"17","author":"Costa","year":"2002","journal-title":"J. Child Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2008.09.060","article-title":"Neurofibromin regulation of ERK signaling modulates GABA release and learning","volume":"135","author":"Cui","year":"2008","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1523\/JNEUROSCI.1605-20.2021","article-title":"Associative Learning Requires Neurofibromin to Modulate GABAergic Inputs to Drosophila Mushroom Bodies","volume":"41","author":"Georganta","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gouzi, J.Y., Moressis, A., Walker, J.A., Apostolopoulou, A.A., Palmer, R.H., Bernards, A., and Skoulakis, E.M.C. (2011). Drosophila Alk Tyrosine Kinase Controls Neurofibromin dependent Growth and Learning. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002281"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.cub.2005.09.043","article-title":"The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1","volume":"15","author":"Li","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"King, L.B., Boto, T., Botero, V., Aviles, A.M., Jomsky, B.M., Joseph, C., Walker, J.A., and Tomchik, S.M. (2020). Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008920"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1126\/science.1063097","article-title":"A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras\/MAPK","volume":"293","author":"Williams","year":"2001","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bai, L., and Sehgal, A. (2015). Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005611"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1080\/17460441.2019.1569624","article-title":"An assessment of the translational relevance of Drosophila in drug discovery","volume":"14","author":"Papanikolopoulou","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1101\/gr.169101","article-title":"A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster","volume":"11","author":"Reiter","year":"2001","journal-title":"Genome Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e51539","DOI":"10.7554\/eLife.51539","article-title":"An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms","volume":"8","author":"Kanca","year":"2019","journal-title":"Elife"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e76077","DOI":"10.7554\/eLife.76077","article-title":"An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination","volume":"11","author":"Kanca","year":"2022","journal-title":"Elife"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.tig.2021.11.006","article-title":"State-of-the-art CRISPR for in vivo and cell-based studies in Drosophila","volume":"38","author":"Zirin","year":"2022","journal-title":"Trends Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/fly.3.1.7726","article-title":"There are many ways to train a fly","volume":"3","author":"Pitman","year":"2009","journal-title":"Fly"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.biopsych.2019.04.029","article-title":"Habituation Learning Is a Widely Affected Mechanism in Drosophila Models of Intellectual Disability and Autism Spectrum Disorders","volume":"86","author":"Fenckova","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7496","DOI":"10.1523\/JNEUROSCI.1055-22.2022","article-title":"Loss of the Schizophrenia-linked Furin protein from Drosophila mushroom body neurons results in antipsychotic-reversible habituation deficits","volume":"42","author":"Foka","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8730","DOI":"10.1523\/JNEUROSCI.0633-19.2019","article-title":"Drosophila Bruton\u2019s Tyrosine Kinase Regulates Habituation Latency and Facilitation in Distinct Mushroom Body Neurons","volume":"39","author":"Roussou","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e39569","DOI":"10.7554\/eLife.39569","article-title":"Temporally specific engagement of distinct neuronal circuits regulating olfactory habituation in Drosophila","volume":"7","author":"Semelidou","year":"2018","journal-title":"Elife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/19336934.2021.1989248","article-title":"How Social Experience and Environment Impacts Behavioural Plasticity in Drosophila","volume":"16","author":"Chen","year":"2022","journal-title":"Fly"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"dmm039180","DOI":"10.1242\/dmm.039180","article-title":"Intellectual disability and autism spectrum disorders \u2018on the fly\u2019: Insights from Drosophila","volume":"12","author":"Krebbers","year":"2019","journal-title":"Dis. Models Mech."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neuroscience.2020.07.034","article-title":"Modelling Learning and Memory in Drosophila to Understand Intellectual Disabilities","volume":"445","author":"Mariano","year":"2020","journal-title":"Neuroscience"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1126\/science.276.5313.791","article-title":"Rescue of a Drosophila NF1 mutant phenotype by protein kinase A","volume":"276","author":"The","year":"1997","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1101\/gad.1466806","article-title":"Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons","volume":"20","author":"Walker","year":"2006","journal-title":"Genes Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10135","DOI":"10.1523\/JNEUROSCI.0283-10.2010","article-title":"A distinct set of Drosophila brain neurons required for neurofibromatosis type 1-dependent learning and memory","volume":"30","author":"Buchanan","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/35002593","article-title":"A neurofibromatosis-1-regulated pathway is required for learning in Drosophila","volume":"403","author":"Guo","year":"2000","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1016\/j.celrep.2018.03.014","article-title":"A Conserved Circadian Function for the Neurofibromatosis 1 Gene","volume":"22","author":"Bai","year":"2018","journal-title":"Cell Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1534\/g3.115.026484","article-title":"Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila","volume":"6","author":"King","year":"2016","journal-title":"G3"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Durkin, J., Poe, A.R., Belfer, S.J., Rodriguez, A., Tang, S.H., Walker, J.A., and Kayser, M.S. (2023). Neurofibromin 1 regulates early developmental sleep in Drosophila. Neurobiol. Sleep Circadian Rhythm., 15.","DOI":"10.1016\/j.nbscr.2023.100101"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107856","DOI":"10.1016\/j.celrep.2020.107856","article-title":"Social Behavioral Deficits with Loss of Neurofibromin Emerge from Peripheral Chemosensory Neuron Dysfunction","volume":"32","author":"Moscato","year":"2020","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9450","DOI":"10.1523\/JNEUROSCI.0562-22.2022","article-title":"Loss of NF1 in Drosophila Larvae Causes Tactile Hypersensitivity and Impaired Synaptic Transmission at the Neuromuscular Junction","volume":"42","author":"Dyson","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0461-22.2023","article-title":"A Targeted, Low-Throughput Compound Screen in a Drosophila Model of Neurofibromatosis Type 1 Identifies Simvastatin and BMS-204352 as Potential Therapies for Autism Spectrum Disorder (ASD)","volume":"10","author":"Dyson","year":"2023","journal-title":"eNeuro"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1038\/s41467-021-24505-x","article-title":"Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila","volume":"12","author":"Botero","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/ng2004","article-title":"Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster","volume":"39","author":"Tong","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_82","first-page":"881","article-title":"Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development","volume":"5","author":"Shin","year":"2012","journal-title":"Dis. Models Mech."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1126\/science.276.5313.795","article-title":"Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides","volume":"276","author":"Guo","year":"1997","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/(SICI)1520-6408(1998)23:4<347::AID-DVG9>3.0.CO;2-C","article-title":"A screen for mutations that prevent lethality caused by expression of activated sevenless and Ras1 in the Drosophila embryo","volume":"23","author":"Maixner","year":"1998","journal-title":"Dev. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejpn.2022.03.004","article-title":"Verbal learning and memory in youth with neurofibromatosis type 1 and plexiform neurofibromas: Relationships with disease severity","volume":"38","author":"Loucas","year":"2022","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/cge.13907","article-title":"A rare disease and education: Neurofibromatosis type 1 decreases educational attainment","volume":"99","author":"Johansson","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/BF01350033","article-title":"Classical conditioning and retention in normal and mutant Drosophila melanogaster","volume":"157","author":"Tully","year":"1985","journal-title":"J. Comp. Physiol. A"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"iyad085","DOI":"10.1093\/genetics\/iyad085","article-title":"Learning and memory using Drosophila melanogaster: A focus on advances made in the fifth decade of research","volume":"224","author":"Davis","year":"2023","journal-title":"Genetics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1101\/lm.5.1.38","article-title":"Tripartite mushroom body architecture revealed by antigenic markers","volume":"5","author":"Crittenden","year":"1998","journal-title":"Learn. Mem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tins.2012.12.002","article-title":"Modeling cognitive dysfunction in neurofibromatosis-1","volume":"36","author":"Gutmann","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/nn.3822","article-title":"Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase","volume":"17","author":"Molosh","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/mp.2015.48","article-title":"HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1","volume":"20","author":"Omrani","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13141","DOI":"10.1073\/pnas.1004829107","article-title":"Neurofibromin regulates corticostriatal inhibitory networks during working memory performance","volume":"107","author":"Shilyansky","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13041-019-0481-0","article-title":"Enriched expression of NF1 in inhibitory neurons in both mouse and human brain","volume":"12","author":"Ryu","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10792","DOI":"10.1523\/JNEUROSCI.1824-17.2017","article-title":"Emerging Mechanisms Underlying Dynamics of GABAergic Synapses","volume":"37","author":"Maffei","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.molmed.2011.03.003","article-title":"The contribution of GABAergic dysfunction to neurodevelopmental disorders","volume":"17","author":"Ramamoorthi","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41583-021-00443-x","article-title":"The role of GABAergic signalling in neurodevelopmental disorders","volume":"22","author":"Tang","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nature711","article-title":"Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1","volume":"415","author":"Costa","year":"2002","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1042\/BJ20090387","article-title":"Anaplastic lymphoma kinase: Signalling in development and disease","volume":"420","author":"Palmer","year":"2009","journal-title":"Biochem. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.bbr.2017.06.024","article-title":"Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice","volume":"332","author":"Weiss","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6852","DOI":"10.1523\/JNEUROSCI.0933-07.2007","article-title":"Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation","volume":"27","author":"Ho","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"16971","DOI":"10.1523\/JNEUROSCI.1756-12.2012","article-title":"Neurofibromin mediates FAK signaling in confining synapse growth at Drosophila neuromuscular junctions","volume":"32","author":"Tsai","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nn.2235","article-title":"The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning","volume":"12","author":"Liu","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.neuron.2007.10.036","article-title":"GABAA receptor RDL inhibits Drosophila olfactory associative learning","volume":"56","author":"Liu","year":"2007","journal-title":"Neuron"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Walker, J.A., Gouzi, J.Y., Long, J.B., Huang, S., Maher, R.C., Xia, H., Khalil, K., Ray, A., Van Vactor, D., and Bernards, R. (2013). Genetic and functional studies implicate synaptic overgrowth and ring gland cAMP\/PKA signaling defects in the Drosophila melanogaster neurofibromatosis-1 growth deficiency. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003958"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/acn3.288","article-title":"A randomized placebo-controlled lovastatin trial for neurobehavioral function in neurofibromatosis I","volume":"3","author":"Bearden","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0076-6879(85)15014-7","article-title":"Diffraction methods for biological macromolecules. Interactive computer graphics: FRODO","volume":"115","author":"Jones","year":"1985","journal-title":"Methods Enzymol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jama.300.3.287","article-title":"Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: A randomized controlled trial","volume":"300","author":"Krab","year":"2008","journal-title":"Jama"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Mainberger, F., Jung, N.H., Zenker, M., Wahllander, U., Freudenberg, L., Langer, S., Berweck, S., Winkler, T., Straube, A., and Heinen, F. (2013). Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1. BMC Neurol., 13.","DOI":"10.1186\/1471-2377-13-131"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1212\/WNL.0000000000003435","article-title":"Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1","volume":"87","author":"Payne","year":"2016","journal-title":"Neurology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13229-018-0190-z","article-title":"Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)","volume":"9","author":"Stivaros","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/S1474-4422(13)70227-8","article-title":"Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): A randomised, placebo-controlled trial","volume":"12","author":"Plasschaert","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/ajmg.b.32280","article-title":"Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1","volume":"168","author":"Plasschaert","year":"2015","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e34497","DOI":"10.7554\/eLife.34497","article-title":"Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier","volume":"7","author":"Qiao","year":"2018","journal-title":"Elife"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0092-8674(01)00245-8","article-title":"NF1 tumor suppressor gene function: Narrowing the GAP","volume":"104","author":"Cichowski","year":"2001","journal-title":"Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e08758","DOI":"10.7554\/eLife.08758","article-title":"A neural command circuit for grooming movement control","volume":"4","author":"Hampel","year":"2015","journal-title":"Elife"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e28804","DOI":"10.7554\/eLife.28804","article-title":"Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila","volume":"6","author":"Hampel","year":"2017","journal-title":"Elife"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e02951","DOI":"10.7554\/eLife.02951","article-title":"A suppression hierarchy among competing motor programs drives sequential grooming in Drosophila","volume":"3","author":"Seeds","year":"2014","journal-title":"Elife"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"190","DOI":"10.5014\/ajot.61.2.190","article-title":"Sensory processing in children with and without autism: A comparative study using the short sensory profile","volume":"61","author":"Tomchek","year":"2007","journal-title":"Am. J. Occup. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"135110","DOI":"10.1016\/j.neulet.2020.135110","article-title":"Crayfish and Drosophila NMJs","volume":"732","author":"Lnenicka","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1073\/pnas.0406164102","article-title":"Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit","volume":"102","author":"Mosca","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Takarae, Y., and Sweeney, J. (2017). Neural Hyperexcitability in Autism Spectrum Disorders. Brain Sci, 7.","DOI":"10.3390\/brainsci7100129"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.1073\/pnas.91.23.10888","article-title":"Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants","volume":"91","author":"Littleton","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1242\/dev.118.4.1077","article-title":"Expression of synaptotagmin in Drosophila reveals transport and localization of synaptic vesicles to the synapse","volume":"118","author":"Littleton","year":"1993","journal-title":"Development"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11065-018-9380-x","article-title":"Social function and autism spectrumbdisorder in children and adults with neurofibromatosis type 1: A systematic review and meta-analysis","volume":"28","author":"Chisholm","year":"2018","journal-title":"Neuropsychol. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/dmcn.14517","article-title":"Social skills and autism spectrum disorder symptoms in children with neurofibromatosis type 1: Evidence for clinical trial outcomes","volume":"62","author":"Payne","year":"2020","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fncir.2019.00057","article-title":"Spontaneous Activity Patterns Are Altered in the Developing Visual Cortex of the Fmr1 Knockout Mouse","volume":"13","author":"Cheyne","year":"2019","journal-title":"Front. Neural Circuits"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2016.05.033","article-title":"Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs","volume":"166","author":"Orefice","year":"2016","journal-title":"Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.neuroscience.2020.01.039","article-title":"Peripheral Somatosensory Neuron Dysfunction: Emerging Roles in Autism Spectrum Disorders","volume":"445","author":"Orefice","year":"2020","journal-title":"Neuroscience"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1213430","DOI":"10.3389\/fneur.2023.1213430","article-title":"Polysomnographic study in pediatric neurofibromatosis type 1","volume":"14","author":"Carotenuto","year":"2023","journal-title":"Front. Neurol."},{"key":"ref_131","first-page":"561","article-title":"Prevalence of sleep disorders in patients with neurofibromatosis type 1","volume":"30","year":"2015","journal-title":"Neurologia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/jpc.14764","article-title":"Perceived fatigue in children and young adults with neurofibromatosis type 1","volume":"56","author":"Vassallo","year":"2020","journal-title":"J. Paediatr. Child Health"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Cirelli, C., and Tononi, G. (2008). Is sleep essential?. PLoS Biol., 6.","DOI":"10.1371\/journal.pbio.0060216"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Jordan, K.W., Carbone, M.A., Yamamoto, A., Morgan, T.J., and Mackay, T.F. (2007). Quantitative genomics of locomotor behavior in Drosophila melanogaster. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-8-r172"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0896-6273(00)80877-6","article-title":"Rest in Drosophila is a sleep-like state","volume":"25","author":"Hendricks","year":"2000","journal-title":"Neuron"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/sleep\/27.4.628","article-title":"Sleep homeostasis in Drosophila melanogaster","volume":"27","author":"Huber","year":"2004","journal-title":"Sleep"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e12816","DOI":"10.1111\/jsr.12816","article-title":"Neurofibromatosis type 1 (Nf1)-mutant mice exhibit increased sleep fragmentation","volume":"28","author":"Anastasaki","year":"2019","journal-title":"J. Sleep Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.bbr.2017.01.003","article-title":"Genetic inhibition of Anaplastic Lymphoma Kinase rescues cognitive impairments in Neurofibromatosis 1 mutant mice","volume":"321","author":"Weiss","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Weiss, J.B., and Raber, J. (2023). Inhibition of Anaplastic Lymphoma Kinase (Alk) as Therapeutic Target to Improve Brain Function in Neurofibromatosis Type 1 (Nf1). Cancers, 15.","DOI":"10.3390\/cancers15184579"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Maurer, G.W., Malita, A., Nagy, S., Koyama, T., Werge, T.M., Halberg, K.A., Texada, M.J., and Rewitz, K. (2020). Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl\/LZTR1 and NF1 in GABAergic sleep control. PLoS Genet., 16.","DOI":"10.1101\/755454"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Brown, E.B., Zhang, J., Lloyd, E., Lanzon, E., Botero, V., Tomchik, S., and Keene, A.C. (2023). Neurofibromin 1 mediates sleep depth in Drosophila. PLoS Genet., 19.","DOI":"10.1371\/journal.pgen.1011049"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/mp.2015.55","article-title":"ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila","volume":"21","author":"Harich","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nn.2860","article-title":"Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine","volume":"14","author":"Shang","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1093\/hmg\/ddv103","article-title":"Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning","volume":"24","author":"Anastasaki","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1523\/JNEUROSCI.3994-09.2010","article-title":"Defective cAMP generation underlies the sensitivity of CNS neurons to neurofibromatosis-1 heterozygosity","volume":"30","author":"Brown","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/ana.23793","article-title":"Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice","volume":"73","author":"Tokuda","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"Rc121","DOI":"10.1523\/JNEUROSCI.21-02-j0001.2001","article-title":"Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain","volume":"21","author":"Volkow","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1001\/jama.2009.1308","article-title":"Evaluating dopamine reward pathway in ADHD: Clinical implications","volume":"302","author":"Volkow","year":"2009","journal-title":"Jama"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jpeds.2021.08.009","article-title":"Birth Characteristics Among Children Diagnosed with Neurofibromatosis Type 1 and Tuberous Sclerosis","volume":"239","author":"Tettamanti","year":"2021","journal-title":"J. Pediatr."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Upadhyaya, M., and Cooper, D. (2012). Neurofibromatosis Type 1. Molecular and Cellular Biology, Springer.","DOI":"10.1007\/978-3-642-32864-0"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Nakayama, J., and Yoshida, Y. (2021). Clinical and Basic Aspects of Neurofibromatosis Type 1, IntechOpen.","DOI":"10.5772\/intechopen.92953"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.brainres.2015.08.025","article-title":"Cerebral glucose metabolism in adults with neurofibromatosis type 1","volume":"1625","author":"Apostolova","year":"2015","journal-title":"Brain Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e28341","DOI":"10.4161\/rdis.28341","article-title":"A Drosophila screen identifies neurofibromatosis-1 genetic modifiers involved in systemic and synaptic growth","volume":"2","author":"Walker","year":"2014","journal-title":"Rare Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1590\/1806-9282.66.5.666","article-title":"Reduced bone mineral content and density in neurofibromatosis type 1 and its association with nutrient intake","volume":"66","author":"Souza","year":"2020","journal-title":"Rev. Assoc. Med. Bras. (1992)"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ajmg.c.32020","article-title":"Bone health in RASopathies","volume":"190","author":"Stevenson","year":"2022","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13023-018-0881-8","article-title":"Craniofacial and oral alterations in patients with Neurofibromatosis 1","volume":"13","author":"Visnapuu","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.clnesp.2019.05.006","article-title":"Increased resting metabolism in neurofibromatosis type 1","volume":"32","author":"Souza","year":"2019","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6712","DOI":"10.1093\/hmg\/ddu389","article-title":"Neuronal NF1\/RAS regulation of cyclic AMP requires atypical PKC activation","volume":"23","author":"Anastasaki","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1093\/hmg\/ddl023","article-title":"Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras","volume":"15","author":"Hannan","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1038\/s41467-022-30466-6","article-title":"Neuronal hyperexcitability drives central and peripheral nervous system tumor progression in models of neurofibromatosis-1","volume":"13","author":"Anastasaki","year":"2022","journal-title":"Nat. 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