[{"quality_controlled":"1","day":"30","has_accepted_license":"1","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","publication_status":"published","publication":"Genes","abstract":[{"text":"Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems","lang":"eng"}],"intvolume":"        12","ec_funded":1,"publication_identifier":{"eissn":["2073-4425"]},"volume":12,"scopus_import":"1","month":"10","citation":{"ieee":"V. Vasic <i>et al.</i>, “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” <i>Genes</i>, vol. 12, no. 11. MDPI, 2021.","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>, vol. 12, no. 11, 1746, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>.","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","ama":"Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. 2021;12(11). doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>","apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., &#38; Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>","chicago":"Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>.","ista":"Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746."},"isi":1,"article_processing_charge":"No","author":[{"last_name":"Vasic","first_name":"Verica","full_name":"Vasic, Verica"},{"full_name":"Jones, Mattson S.O.","last_name":"Jones","first_name":"Mattson S.O."},{"last_name":"Haslinger","first_name":"Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","full_name":"Haslinger, Denise"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa"},{"first_name":"Michael J.","last_name":"Schmeisser","full_name":"Schmeisser, Michael J."},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Chiocchetti, Andreas G.","last_name":"Chiocchetti","first_name":"Andreas G."}],"project":[{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232"}],"language":[{"iso":"eng"}],"acknowledgement":"This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811); Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was also supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24) both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes for her support in preparing this manuscript.","oa":1,"date_updated":"2025-04-15T07:29:28Z","external_id":{"isi":["000834044200002"]},"department":[{"_id":"GaNo"}],"alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"article_number":"1746","_id":"10281","file":[{"relation":"main_file","date_created":"2022-05-16T07:02:27Z","content_type":"application/pdf","success":1,"checksum":"256cb832a9c3051c7dc741f6423b8cbd","access_level":"open_access","date_updated":"2022-05-16T07:02:27Z","creator":"dernst","file_size":1335308,"file_name":"2021_Genes_Vasic.pdf","file_id":"11380"}],"file_date_updated":"2022-05-16T07:02:27Z","oa_version":"Published Version","doi":"10.3390/genes12111746","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","article_type":"original","publisher":"MDPI","year":"2021","license":"https://creativecommons.org/licenses/by/4.0/","ddc":["570"],"issue":"11","status":"public","date_published":"2021-10-30T00:00:00Z","date_created":"2021-11-14T23:01:24Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"month":"08","scopus_import":"1","volume":12,"publication_identifier":{"eissn":["2073-4425"]},"oa":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"715257","_id":"250BDE62-B435-11E9-9278-68D0E5697425","name":"Prevalence and Influence of Sexual Antagonism on Genome Evolution","call_identifier":"H2020"}],"author":[{"last_name":"Picard","first_name":"Marion A L","id":"2C921A7A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8101-2518","full_name":"Picard, Marion A L"},{"orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","last_name":"Vicoso","first_name":"Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Stéphanie","last_name":"Bertrand","full_name":"Bertrand, Stéphanie"},{"full_name":"Escriva, Hector","first_name":"Hector","last_name":"Escriva"}],"citation":{"apa":"Picard, M. A. L., Vicoso, B., Bertrand, S., &#38; Escriva, H. (2021). Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12081136\">https://doi.org/10.3390/genes12081136</a>","ama":"Picard MAL, Vicoso B, Bertrand S, Escriva H. Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict. <i>Genes</i>. 2021;12(8). doi:<a href=\"https://doi.org/10.3390/genes12081136\">10.3390/genes12081136</a>","chicago":"Picard, Marion A L, Beatriz Vicoso, Stéphanie Bertrand, and Hector Escriva. “Diversity of Modes of Reproduction and Sex Determination Systems in Invertebrates, and the Putative Contribution of Genetic Conflict.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12081136\">https://doi.org/10.3390/genes12081136</a>.","ista":"Picard MAL, Vicoso B, Bertrand S, Escriva H. 2021. Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict. Genes. 12(8), 1136.","short":"M.A.L. Picard, B. Vicoso, S. Bertrand, H. Escriva, Genes 12 (2021).","ieee":"M. A. L. Picard, B. Vicoso, S. Bertrand, and H. Escriva, “Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict,” <i>Genes</i>, vol. 12, no. 8. MDPI, 2021.","mla":"Picard, Marion A. L., et al. “Diversity of Modes of Reproduction and Sex Determination Systems in Invertebrates, and the Putative Contribution of Genetic Conflict.” <i>Genes</i>, vol. 12, no. 8, 1136, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12081136\">10.3390/genes12081136</a>."},"article_processing_charge":"Yes","isi":1,"day":"01","quality_controlled":"1","ec_funded":1,"intvolume":"        12","abstract":[{"lang":"eng","text":"About eight million animal species are estimated to live on Earth, and all except those belonging to one subphylum are invertebrates. Invertebrates are incredibly diverse in their morphologies, life histories, and in the range of the ecological niches that they occupy. A great variety of modes of reproduction and sex determination systems is also observed among them, and their mosaic-distribution across the phylogeny shows that transitions between them occur frequently and rapidly. Genetic conflict in its various forms is a long-standing theory to explain what drives those evolutionary transitions. Here, we review (1) the different modes of reproduction among invertebrate species, highlighting sexual reproduction as the probable ancestral state; (2) the paradoxical diversity of sex determination systems; (3) the different types of genetic conflicts that could drive the evolution of such different systems."}],"publication":"Genes","title":"Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict","publication_status":"published","has_accepted_license":"1","pmid":1,"issue":"8","ddc":["570"],"year":"2021","publisher":"MDPI","article_type":"review","type":"journal_article","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2021-08-15T22:01:27Z","date_published":"2021-08-01T00:00:00Z","status":"public","department":[{"_id":"BeVi"}],"external_id":{"pmid":["34440310"],"isi":["000690475900001"]},"date_updated":"2026-04-02T14:05:14Z","doi":"10.3390/genes12081136","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa_version":"Published Version","file_date_updated":"2021-08-16T09:49:35Z","file":[{"creator":"asandaue","file_size":2297655,"file_name":"2021_Genes_Picard.pdf","file_id":"9926","checksum":"744e60e56d290a96da3c91a9779f886f","access_level":"open_access","date_updated":"2021-08-16T09:49:35Z","date_created":"2021-08-16T09:49:35Z","success":1,"content_type":"application/pdf","relation":"main_file"}],"_id":"9908","article_number":"1136"},{"department":[{"_id":"JiFr"}],"external_id":{"isi":["000690558000001"]},"date_updated":"2026-04-02T13:57:06Z","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"doi":"10.3390/genes12081141","oa_version":"Published Version","file_date_updated":"2021-08-16T09:02:40Z","_id":"9909","article_number":"1141","file":[{"relation":"main_file","date_created":"2021-08-16T09:02:40Z","content_type":"application/pdf","success":1,"access_level":"open_access","date_updated":"2021-08-16T09:02:40Z","checksum":"3d99535618cf9a5b14d264408fa52e97","file_size":1340305,"file_name":"2021_Genes_Zeng.pdf","file_id":"9919","creator":"asandaue"}],"issue":"8","ddc":["580","570"],"year":"2021","publisher":"MDPI","article_type":"original","type":"journal_article","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2021-08-15T22:01:28Z","date_published":"2021-07-27T00:00:00Z","status":"public","day":"27","quality_controlled":"1","intvolume":"        12","abstract":[{"lang":"eng","text":"Roots are composed of different root types and, in the dicotyledonous Arabidopsis, typically consist of a primary root that branches into lateral roots. Adventitious roots emerge from non-root tissue and are formed upon wounding or other types of abiotic stress. Here, we investigated adventitious root (AR) formation in Arabidopsis hypocotyls under conditions of altered abscisic acid (ABA) signaling. Exogenously applied ABA suppressed AR formation at 0.25 µM or higher doses. AR formation was less sensitive to the synthetic ABA analog pyrabactin (PB). However, PB was a more potent inhibitor at concentrations above 1 µM, suggesting that it was more selective in triggering a root inhibition response. Analysis of a series of phosphonamide and phosphonate pyrabactin analogs suggested that adventitious root formation and lateral root branching are differentially regulated by ABA signaling. ABA biosynthesis and signaling mutants affirmed a general inhibitory role of ABA and point to PYL1 and PYL2 as candidate ABA receptors that regulate AR inhibition."}],"publication":"Genes","title":"Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling","publication_status":"published","has_accepted_license":"1","month":"07","scopus_import":"1","volume":12,"publication_identifier":{"eissn":["2073-4425"]},"oa":1,"acknowledgement":"We thank S. Cutler (Riverside, USA) for providing the ABA biosynthesis mutants and ABA signaling mutants.","language":[{"iso":"eng"}],"author":[{"full_name":"Zeng, Yinwei","first_name":"Yinwei","last_name":"Zeng"},{"first_name":"Inge","id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","last_name":"Verstraeten","full_name":"Verstraeten, Inge","orcid":"0000-0001-7241-2328"},{"full_name":"Trinh, Hoang Khai","first_name":"Hoang Khai","last_name":"Trinh"},{"last_name":"Heugebaert","first_name":"Thomas","full_name":"Heugebaert, Thomas"},{"last_name":"Stevens","first_name":"Christian V.","full_name":"Stevens, Christian V."},{"full_name":"Garcia-Maquilon, Irene","first_name":"Irene","last_name":"Garcia-Maquilon"},{"last_name":"Rodriguez","first_name":"Pedro L.","full_name":"Rodriguez, Pedro L."},{"full_name":"Vanneste, Steffen","first_name":"Steffen","last_name":"Vanneste"},{"first_name":"Danny","last_name":"Geelen","full_name":"Geelen, Danny"}],"citation":{"short":"Y. Zeng, I. Verstraeten, H.K. Trinh, T. Heugebaert, C.V. Stevens, I. Garcia-Maquilon, P.L. Rodriguez, S. Vanneste, D. Geelen, Genes 12 (2021).","chicago":"Zeng, Yinwei, Inge Verstraeten, Hoang Khai Trinh, Thomas Heugebaert, Christian V. Stevens, Irene Garcia-Maquilon, Pedro L. Rodriguez, Steffen Vanneste, and Danny Geelen. “Arabidopsis Hypocotyl Adventitious Root Formation Is Suppressed by ABA Signaling.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12081141\">https://doi.org/10.3390/genes12081141</a>.","ista":"Zeng Y, Verstraeten I, Trinh HK, Heugebaert T, Stevens CV, Garcia-Maquilon I, Rodriguez PL, Vanneste S, Geelen D. 2021. Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling. Genes. 12(8), 1141.","apa":"Zeng, Y., Verstraeten, I., Trinh, H. K., Heugebaert, T., Stevens, C. V., Garcia-Maquilon, I., … Geelen, D. (2021). Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12081141\">https://doi.org/10.3390/genes12081141</a>","ama":"Zeng Y, Verstraeten I, Trinh HK, et al. Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling. <i>Genes</i>. 2021;12(8). doi:<a href=\"https://doi.org/10.3390/genes12081141\">10.3390/genes12081141</a>","mla":"Zeng, Yinwei, et al. “Arabidopsis Hypocotyl Adventitious Root Formation Is Suppressed by ABA Signaling.” <i>Genes</i>, vol. 12, no. 8, 1141, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12081141\">10.3390/genes12081141</a>.","ieee":"Y. Zeng <i>et al.</i>, “Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling,” <i>Genes</i>, vol. 12, no. 8. MDPI, 2021."},"article_processing_charge":"Yes","isi":1}]