--- _id: '11160' abstract: - lang: eng text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com. article_number: '110615' article_processing_charge: Yes article_type: original author: - first_name: Carlo Emanuele full_name: Villa, Carlo Emanuele last_name: Villa - first_name: Cristina full_name: Cheroni, Cristina last_name: Cheroni - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Alejandro full_name: López-Tóbon, Alejandro last_name: López-Tóbon - first_name: Bárbara full_name: Oliveira, Bárbara id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87 last_name: Oliveira - first_name: Roberto full_name: Sacco, Roberto id: 42C9F57E-F248-11E8-B48F-1D18A9856A87 last_name: Sacco - first_name: Aysan Çerağ full_name: Yahya, Aysan Çerağ id: 365A65F8-F248-11E8-B48F-1D18A9856A87 last_name: Yahya - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Michele full_name: Gabriele, Michele last_name: Gabriele - first_name: Mojtaba full_name: Tavakoli, Mojtaba id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87 last_name: Tavakoli orcid: 0000-0002-7667-6854 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Mariano full_name: Gabitto, Mariano last_name: Gabitto - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Giuseppe full_name: Testa, Giuseppe last_name: Testa - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615 apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615 chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615. ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022. ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615. mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615. short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022). date_created: 2022-04-15T09:03:10Z date_published: 2022-04-05T00:00:00Z date_updated: 2024-03-27T23:30:44Z day: '05' ddc: - '570' department: - _id: JoDa - _id: GaNo doi: 10.1016/j.celrep.2022.110615 ec_funded: 1 external_id: isi: - '000785983900003' pmid: - '35385734' file: - access_level: open_access checksum: b4e8d68f0268dec499af333e6fd5d8e1 content_type: application/pdf creator: dernst date_created: 2022-04-15T09:06:25Z date_updated: 2022-04-15T09:06:25Z file_id: '11164' file_name: 2022_CellReports_Villa.pdf file_size: '7808644' relation: main_file success: 1 file_date_updated: 2022-04-15T09:06:25Z has_accepted_license: '1' intvolume: ' 39' isi: 1 issue: '1' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 2690FEAC-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I04205 name: Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy publication: Cell Reports publication_identifier: issn: - 2211-1247 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '12364' relation: dissertation_contains status: public status: public title: CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories tmp: 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) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 39 year: '2022' ... --- _id: '9429' abstract: - lang: eng text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs. acknowledged_ssus: - _id: PreCl acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27). article_number: '3058' article_processing_charge: No article_type: original author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Georgi A full_name: Dimchev, Georgi A id: 38C393BE-F248-11E8-B48F-1D18A9856A87 last_name: Dimchev orcid: 0000-0001-8370-6161 - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x. ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021. ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058. mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x. short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021). date_created: 2021-05-28T11:49:46Z date_published: 2021-05-24T00:00:00Z date_updated: 2024-03-27T23:30:23Z day: '24' ddc: - '572' department: - _id: GaNo - _id: JoDa - _id: FlSc - _id: MiSi - _id: LifeSc - _id: Bio doi: 10.1038/s41467-021-23123-x ec_funded: 1 external_id: isi: - '000658769900010' file: - access_level: open_access checksum: 337e0f7959c35ec959984cacdcb472ba content_type: application/pdf creator: kschuh date_created: 2021-05-28T12:39:43Z date_updated: 2021-05-28T12:39:43Z file_id: '9430' file_name: 2021_NatureCommunications_Morandell.pdf file_size: 9358599 relation: main_file success: 1 file_date_updated: 2021-05-28T12:39:43Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: press_release url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/ record: - id: '7800' relation: earlier_version status: public - id: '12401' relation: dissertation_contains status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development tmp: 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) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '8620' abstract: - lang: eng text: "The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages." acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell citation: ama: Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620 apa: Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620 chicago: Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620. ieee: J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020. ista: Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. mla: Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620. short: J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020. date_created: 2020-10-07T14:53:13Z date_published: 2020-10-12T00:00:00Z date_updated: 2023-09-07T13:22:14Z day: '12' ddc: - '610' degree_awarded: PhD department: - _id: GaNo doi: 10.15479/AT:ISTA:8620 file: - access_level: open_access checksum: 7ee83e42de3e5ce2fedb44dff472f75f content_type: application/pdf creator: jmorande date_created: 2020-10-07T14:41:49Z date_updated: 2021-10-16T22:30:04Z embargo: 2021-10-15 file_id: '8621' file_name: Jasmin_Morandell_Thesis-2020_final.pdf file_size: 16155786 relation: main_file - access_level: closed checksum: 5e0464af453734210ce7aab7b4a92e3a content_type: application/x-zip-compressed creator: jmorande date_created: 2020-10-07T14:45:07Z date_updated: 2021-10-16T22:30:04Z embargo_to: open_access file_id: '8622' file_name: Jasmin_Morandell_Thesis-2020_final.zip file_size: 24344152 relation: source_file file_date_updated: 2021-10-16T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '138' project: - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7800' relation: part_of_dissertation status: public - id: '8131' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 title: Illuminating the role of Cul3 in autism spectrum disorder pathogenesis type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7800' abstract: - lang: eng text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages. acknowledged_ssus: - _id: PreCl article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 . ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory. ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 . mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 . short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.). date_created: 2020-05-05T14:31:33Z date_published: 2020-01-11T00:00:00Z date_updated: 2024-03-27T23:30:14Z day: '11' ddc: - '570' department: - _id: JoDa - _id: GaNo - _id: LifeSc doi: '10.1101/2020.01.10.902064 ' file: - access_level: open_access checksum: c6799ab5daba80efe8e2ed63c15f8c81 content_type: application/pdf creator: rsix date_created: 2020-05-05T14:31:19Z date_updated: 2020-07-14T12:48:03Z file_id: '7801' file_name: 2020.01.10.902064v1.full.pdf file_size: 2931370 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Preprint project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '9429' relation: later_version status: public - id: '8620' relation: dissertation_contains status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8131' abstract: - lang: eng text: The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004 apa: Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004 chicago: Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development. Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004. ieee: B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020. ista: Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137. mla: Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004. short: B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137. date_created: 2020-07-19T22:00:58Z date_published: 2020-12-01T00:00:00Z date_updated: 2024-03-27T23:30:14Z day: '01' ddc: - '570' department: - _id: GaNo doi: 10.1016/j.gde.2020.06.004 ec_funded: 1 external_id: isi: - '000598918900019' pmid: - '32659636' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T06:47:45Z date_updated: 2020-07-22T06:47:45Z file_id: '8146' file_name: 2020_CurrentOpGenetics_Basilico.pdf file_size: 1381545 relation: main_file success: 1 file_date_updated: 2020-07-22T06:47:45Z has_accepted_license: '1' intvolume: ' 65' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 126-137 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy publication: Current Opinion in Genetics and Development publication_identifier: eissn: - '18790380' issn: - 0959437X publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '8620' relation: dissertation_contains status: public scopus_import: '1' status: public title: Molecular mechanisms for targeted ASD treatments tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 65 year: '2020' ... --- _id: '7415' article_processing_charge: No article_type: original author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040 apa: Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040 chicago: Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040. ieee: J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019. ista: Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 29(Supplement 6), S11–S12. mla: Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040. short: J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12. date_created: 2020-01-30T10:07:41Z date_published: 2019-12-13T00:00:00Z date_updated: 2023-09-07T14:56:17Z day: '13' department: - _id: GaNo - _id: LifeSc doi: 10.1016/j.euroneuro.2019.09.040 external_id: isi: - '000502657500021' intvolume: ' 29' isi: 1 issue: Supplement 6 language: - iso: eng month: '12' oa_version: None page: S11-S12 publication: European Neuropsychopharmacology publication_identifier: issn: - 0924-977X publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 29 year: '2019' ... --- _id: '3' abstract: - lang: eng text: SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder. acknowledged_ssus: - _id: M-Shop - _id: PreCl acknowledgement: This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N. article_processing_charge: No article_type: original author: - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Niccoló full_name: Arecco, Niccoló last_name: Arecco - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Charles full_name: Girardot, Charles last_name: Girardot - first_name: Eva full_name: Käsper, Eva last_name: Käsper - first_name: Alena full_name: Kozlova, Alena id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D last_name: Kozlova - first_name: Kasumi full_name: Kishi, Kasumi id: 3065DFC4-F248-11E8-B48F-1D18A9856A87 last_name: Kishi - first_name: Ilaria full_name: Chiaradia, Ilaria id: B6467F20-02D0-11E9-BDA5-E960C241894A last_name: Chiaradia orcid: 0000-0002-9529-4464 - first_name: Kyung full_name: Noh, Kyung last_name: Noh - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2 apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2 chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2. ieee: E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018. ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727. mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2. short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727. date_created: 2018-12-11T11:44:05Z date_published: 2018-11-19T00:00:00Z date_updated: 2024-03-27T23:30:44Z day: '19' ddc: - '570' department: - _id: GaNo - _id: EdHa doi: 10.1038/s41593-018-0266-2 external_id: isi: - '000451324700010' file: - access_level: open_access checksum: 60abd0f05b7cdc08a6b0ec460884084f content_type: application/pdf creator: dernst date_created: 2019-04-09T07:41:57Z date_updated: 2020-07-14T12:45:58Z file_id: '6255' file_name: 2017_NatureNeuroscience_Deliu.pdf file_size: 8167169 relation: main_file file_date_updated: 2020-07-14T12:45:58Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '12' language: - iso: eng month: '11' oa: 1 oa_version: Submitted Version page: 1717 - 1727 project: - _id: 254BA948-B435-11E9-9278-68D0E5697425 grant_number: '401299' name: Probing development and reversibility of autism spectrum disorders publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '8054' pubrep_id: '1071' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/ record: - id: '6074' relation: popular_science status: public - id: '12364' relation: dissertation_contains status: public scopus_import: '1' status: public title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 21 year: '2018' ... --- _id: '1106' abstract: - lang: eng text: Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect. author: - first_name: Mala full_name: Isrie, Mala last_name: Isrie - first_name: Martin full_name: Breuss, Martin last_name: Breuss - first_name: Guoling full_name: Tian, Guoling last_name: Tian - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Francesca full_name: Cristofoli, Francesca last_name: Cristofoli - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Zachari A full_name: Kupchinsky, Zachari A last_name: Kupchinsky - first_name: Alejandro full_name: Sifrim, Alejandro last_name: Sifrim - first_name: Celia full_name: Rodriguez Rodriguez, Celia last_name: Rodriguez Rodriguez - first_name: Elena P full_name: Dapena, Elena P last_name: Dapena - first_name: Kurston full_name: Doonanco, Kurston last_name: Doonanco - first_name: Norma full_name: Leonard, Norma last_name: Leonard - first_name: Faten full_name: Tinsa, Faten last_name: Tinsa - first_name: Stéphanie full_name: Moortgat, Stéphanie last_name: Moortgat - first_name: Hakan full_name: Ulucan, Hakan last_name: Ulucan - first_name: Erkan full_name: Koparir, Erkan last_name: Koparir - first_name: Ender full_name: Karaca, Ender last_name: Karaca - first_name: Nicholas full_name: Katsanis, Nicholas last_name: Katsanis - first_name: Valeria full_name: Marton, Valeria last_name: Marton - first_name: Joris R full_name: Vermeesch, Joris R last_name: Vermeesch - first_name: Erica E full_name: Davis, Erica E last_name: Davis - first_name: Nicholas J full_name: Cowan, Nicholas J last_name: Cowan - first_name: David full_name: Keays, David last_name: Keays - first_name: Hilde full_name: Van Esch, Hilde last_name: Van Esch citation: ama: Isrie M, Breuss M, Tian G, et al. Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. 2015;97(6):790-800. doi:10.1016/j.ajhg.2015.10.014 apa: Isrie, M., Breuss, M., Tian, G., Hansen, A. H., Cristofoli, F., Morandell, J., … Van Esch, H. (2015). Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. Cell Press. https://doi.org/10.1016/j.ajhg.2015.10.014 chicago: Isrie, Mala, Martin Breuss, Guoling Tian, Andi H Hansen, Francesca Cristofoli, Jasmin Morandell, Zachari A Kupchinsky, et al. “Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.” The American Journal of Human Genetics. Cell Press, 2015. https://doi.org/10.1016/j.ajhg.2015.10.014. ieee: M. Isrie et al., “Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type,” The American Journal of Human Genetics, vol. 97, no. 6. Cell Press, pp. 790–800, 2015. ista: Isrie M, Breuss M, Tian G, Hansen AH, Cristofoli F, Morandell J, Kupchinsky ZA, Sifrim A, Rodriguez Rodriguez C, Dapena EP, Doonanco K, Leonard N, Tinsa F, Moortgat S, Ulucan H, Koparir E, Karaca E, Katsanis N, Marton V, Vermeesch JR, Davis EE, Cowan NJ, Keays D, Van Esch H. 2015. Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. 97(6), 790–800. mla: Isrie, Mala, et al. “Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.” The American Journal of Human Genetics, vol. 97, no. 6, Cell Press, 2015, pp. 790–800, doi:10.1016/j.ajhg.2015.10.014. short: M. Isrie, M. Breuss, G. Tian, A.H. Hansen, F. Cristofoli, J. Morandell, Z.A. Kupchinsky, A. Sifrim, C. Rodriguez Rodriguez, E.P. Dapena, K. Doonanco, N. Leonard, F. Tinsa, S. Moortgat, H. Ulucan, E. Koparir, E. Karaca, N. Katsanis, V. Marton, J.R. Vermeesch, E.E. Davis, N.J. Cowan, D. Keays, H. Van Esch, The American Journal of Human Genetics 97 (2015) 790–800. date_created: 2018-12-11T11:50:11Z date_published: 2015-12-03T00:00:00Z date_updated: 2021-01-12T06:48:19Z day: '03' doi: 10.1016/j.ajhg.2015.10.014 extern: '1' intvolume: ' 97' issue: '6' language: - iso: eng month: '12' oa_version: None page: 790 - 800 publication: The American Journal of Human Genetics publication_status: published publisher: Cell Press publist_id: '6264' quality_controlled: '1' status: public title: Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 97 year: '2015' ...