---
_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).
corr_author: '1'
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2026-04-27T22:30:30Z
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:
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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: '18681'
relation: dissertation_contains
status: public
- id: '18674'
relation: dissertation_contains
status: public
- id: '12364'
relation: dissertation_contains
status: public
scopus_import: '1'
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).
corr_author: '1'
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2026-04-27T22:30:54Z
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:
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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
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file_date_updated: 2021-05-28T12:39:43Z
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keyword:
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language:
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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
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-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:
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relation: dissertation_contains
status: public
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
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'
...
---
OA_place: publisher
_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.
corr_author: '1'
date_created: 2020-10-07T14:53:13Z
date_published: 2020-10-12T00:00:00Z
date_updated: 2026-04-14T09:07:16Z
day: '12'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:8620
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page: '138'
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
cells in autism and epilepsy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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relation: part_of_dissertation
status: public
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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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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.).
corr_author: '1'
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2026-04-27T22:30:53Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
file:
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checksum: c6799ab5daba80efe8e2ed63c15f8c81
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date_updated: 2020-07-14T12:48:03Z
file_id: '7801'
file_name: 2020.01.10.902064v1.full.pdf
file_size: 2931370
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file_date_updated: 2020-07-14T12:48:03Z
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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
name: Molecular Drug Targets
publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
related_material:
record:
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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.
corr_author: '1'
date_created: 2020-07-19T22:00:58Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2026-04-27T22:30:53Z
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:
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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
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
cells in autism and epilepsy
publication: Current Opinion in Genetics and Development
publication_identifier:
eissn:
- 1879-0380
issn:
- 0959-437X
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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
orcid: 0000-0001-6060-4795
- 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.
corr_author: '1'
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2026-04-27T22:30:30Z
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.
article_processing_charge: No
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: 2025-09-23T09:38:06Z
day: '03'
doi: 10.1016/j.ajhg.2015.10.014
extern: '1'
external_id:
isi:
- '000368437900002'
intvolume: ' 97'
isi: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 97
year: '2015'
...