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