---
_id: '412'
abstract:
- lang: eng
text: Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which
cargoes and lipids are internalized from the plasma membrane into vesicles coated
with clathrin and adaptor proteins. CME is essential for many developmental and
physiological processes in plants, but its underlying mechanism is not well characterised
compared to that in yeast and animal systems. Here, we searched for new factors
involved in CME in Arabidopsis thaliana by performing Tandem Affinity Purification
of proteins that interact with clathrin light chain, a principal component of
the clathrin coat. Among the confirmed interactors, we found two putative homologues
of the clathrin-coat uncoating factor auxilin previously described in non-plant
systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in A. thaliana caused
an arrest of seedling growth and development. This was concomitant with inhibited
endocytosis due to blocking of clathrin recruitment after the initial step of
adaptor protein binding to the plasma membrane. By contrast, auxilin-like(1/2)
loss-of-function lines did not present endocytosis-related developmental or cellular
phenotypes under normal growth conditions. This work contributes to the on-going
characterization of the endocytotic machinery in plants and provides a robust
tool for conditionally and specifically interfering with CME in A. thaliana.
acknowledgement: We thank James Matthew Watson, Monika Borowska, and Peggy Stolt-Bergner
at ProTech Facility of the Vienna Biocenter Core Facilities for the CRISPR/CAS9
construct; Anna Müller for assistance with molecular cloning; Sebastian Bednarek,
Liwen Jiang, and Daniël Van Damme for sharing published material; Matyáš Fendrych,
Daniël Van Damme, and Lindy Abas for valuable discussions; and Martine De Cock for
help with correcting the manuscript. This work was supported by the European Research
Council under the European Union Seventh Framework Programme (FP7/2007-2013)/ERC
Grant 282300 and by the Ministry of Education of the Czech Republic/MŠMT project
NPUI-LO1417.
article_processing_charge: No
article_type: original
author:
- first_name: Maciek
full_name: Adamowski, Maciek
id: 45F536D2-F248-11E8-B48F-1D18A9856A87
last_name: Adamowski
orcid: 0000-0001-6463-5257
- first_name: Madhumitha
full_name: Narasimhan, Madhumitha
id: 44BF24D0-F248-11E8-B48F-1D18A9856A87
last_name: Narasimhan
orcid: 0000-0002-8600-0671
- first_name: Urszula
full_name: Kania, Urszula
id: 4AE5C486-F248-11E8-B48F-1D18A9856A87
last_name: Kania
- first_name: Matous
full_name: Glanc, Matous
id: 1AE1EA24-02D0-11E9-9BAA-DAF4881429F2
last_name: Glanc
orcid: 0000-0003-0619-7783
- first_name: Geert
full_name: De Jaeger, Geert
last_name: De Jaeger
- first_name: Jirí
full_name: Friml, Jirí
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Adamowski M, Narasimhan M, Kania U, Glanc M, De Jaeger G, Friml J. A functional
study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors in Arabidopsis.
The Plant Cell. 2018;30(3):700-716. doi:10.1105/tpc.17.00785
apa: Adamowski, M., Narasimhan, M., Kania, U., Glanc, M., De Jaeger, G., & Friml,
J. (2018). A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating
factors in Arabidopsis. The Plant Cell. American Society of Plant Biologists.
https://doi.org/10.1105/tpc.17.00785
chicago: Adamowski, Maciek, Madhumitha Narasimhan, Urszula Kania, Matous Glanc,
Geert De Jaeger, and Jiří Friml. “A Functional Study of AUXILIN LIKE1 and 2 Two
Putative Clathrin Uncoating Factors in Arabidopsis.” The Plant Cell. American
Society of Plant Biologists, 2018. https://doi.org/10.1105/tpc.17.00785.
ieee: M. Adamowski, M. Narasimhan, U. Kania, M. Glanc, G. De Jaeger, and J. Friml,
“A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors
in Arabidopsis,” The Plant Cell, vol. 30, no. 3. American Society of Plant
Biologists, pp. 700–716, 2018.
ista: Adamowski M, Narasimhan M, Kania U, Glanc M, De Jaeger G, Friml J. 2018. A
functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors
in Arabidopsis. The Plant Cell. 30(3), 700–716.
mla: Adamowski, Maciek, et al. “A Functional Study of AUXILIN LIKE1 and 2 Two Putative
Clathrin Uncoating Factors in Arabidopsis.” The Plant Cell, vol. 30, no.
3, American Society of Plant Biologists, 2018, pp. 700–16, doi:10.1105/tpc.17.00785.
short: M. Adamowski, M. Narasimhan, U. Kania, M. Glanc, G. De Jaeger, J. Friml,
The Plant Cell 30 (2018) 700–716.
date_created: 2018-12-11T11:46:20Z
date_published: 2018-04-09T00:00:00Z
date_updated: 2024-03-28T23:30:06Z
day: '09'
ddc:
- '580'
department:
- _id: JiFr
doi: 10.1105/tpc.17.00785
ec_funded: 1
external_id:
isi:
- '000429441400018'
pmid:
- '29511054'
file:
- access_level: open_access
checksum: 4e165e653b67d3f0684697f21aace5a1
content_type: application/pdf
creator: dernst
date_created: 2022-05-23T09:12:38Z
date_updated: 2022-05-23T09:12:38Z
file_id: '11406'
file_name: 2018_PlantCell_Adamowski.pdf
file_size: 4407538
relation: main_file
success: 1
file_date_updated: 2022-05-23T09:12:38Z
has_accepted_license: '1'
intvolume: ' 30'
isi: 1
issue: '3'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '04'
oa: 1
oa_version: Published Version
page: 700 - 716
pmid: 1
project:
- _id: 25716A02-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '282300'
name: Polarity and subcellular dynamics in plants
publication: The Plant Cell
publication_identifier:
eissn:
- 1532-298X
issn:
- 1040-4651
publication_status: published
publisher: American Society of Plant Biologists
publist_id: '7417'
quality_controlled: '1'
related_material:
record:
- id: '6269'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors
in Arabidopsis
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2018'
...
---
_id: '5914'
abstract:
- lang: eng
text: With the advent of optogenetics, it became possible to change the activity
of a targeted population of neurons in a temporally controlled manner. To combine
the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics,
we have developed a closed-loop recording system that allows for the actual electrophysiological
signal to be used as a trigger for the laser light mediating the optogenetic intervention.
We have optimized the weight, size, and shape of the corresponding implant to
make it compatible with the size, force, and movements of a behaving mouse, and
we have shown that the system can efficiently block sharp wave ripple (SWR) events
using those events themselves as a trigger. To demonstrate the full potential
of the optogenetic recording system we present a pilot study addressing the contribution
of SWR events to learning in a complex behavioral task.
article_number: e0087
article_processing_charge: No
author:
- first_name: Dámaris K
full_name: Rangel Guerrero, Dámaris K
id: 4871BCE6-F248-11E8-B48F-1D18A9856A87
last_name: Rangel Guerrero
orcid: 0000-0002-8602-4374
- first_name: James G.
full_name: Donnett, James G.
last_name: Donnett
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
- first_name: Krisztián
full_name: Kovács, Krisztián
id: 2AB5821E-F248-11E8-B48F-1D18A9856A87
last_name: Kovács
orcid: 0000-0001-6251-1007
citation:
ama: 'Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. Tetrode recording
from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop
optogenetics: A technique to study the contribution of Hippocampal SWR events
to learning. eNeuro. 2018;5(4). doi:10.1523/ENEURO.0087-18.2018'
apa: 'Rangel Guerrero, D. K., Donnett, J. G., Csicsvari, J. L., & Kovács, K.
(2018). Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal
SWR events to learning. ENeuro. Society of Neuroscience. https://doi.org/10.1523/ENEURO.0087-18.2018'
chicago: 'Rangel Guerrero, Dámaris K, James G. Donnett, Jozsef L Csicsvari, and
Krisztián Kovács. “Tetrode Recording from the Hippocampus of Behaving Mice Coupled
with Four-Point-Irradiation Closed-Loop Optogenetics: A Technique to Study the
Contribution of Hippocampal SWR Events to Learning.” ENeuro. Society of
Neuroscience, 2018. https://doi.org/10.1523/ENEURO.0087-18.2018.'
ieee: 'D. K. Rangel Guerrero, J. G. Donnett, J. L. Csicsvari, and K. Kovács, “Tetrode
recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal
SWR events to learning,” eNeuro, vol. 5, no. 4. Society of Neuroscience,
2018.'
ista: 'Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. 2018. Tetrode recording
from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop
optogenetics: A technique to study the contribution of Hippocampal SWR events
to learning. eNeuro. 5(4), e0087.'
mla: 'Rangel Guerrero, Dámaris K., et al. “Tetrode Recording from the Hippocampus
of Behaving Mice Coupled with Four-Point-Irradiation Closed-Loop Optogenetics:
A Technique to Study the Contribution of Hippocampal SWR Events to Learning.”
ENeuro, vol. 5, no. 4, e0087, Society of Neuroscience, 2018, doi:10.1523/ENEURO.0087-18.2018.'
short: D.K. Rangel Guerrero, J.G. Donnett, J.L. Csicsvari, K. Kovács, ENeuro 5 (2018).
date_created: 2019-02-03T22:59:16Z
date_published: 2018-07-27T00:00:00Z
date_updated: 2024-03-28T23:30:10Z
day: '27'
ddc:
- '570'
department:
- _id: JoCs
doi: 10.1523/ENEURO.0087-18.2018
ec_funded: 1
external_id:
isi:
- '000443994700007'
file:
- access_level: open_access
checksum: f4915d45fc7ad4648b7b7a13fdecca01
content_type: application/pdf
creator: dernst
date_created: 2019-02-05T12:48:36Z
date_updated: 2020-07-14T12:47:13Z
file_id: '5921'
file_name: 2018_ENeuro_Guerrero.pdf
file_size: 3746884
relation: main_file
file_date_updated: 2020-07-14T12:47:13Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
issue: '4'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 257D4372-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I2072-B27
name: Interneuron plasticity during spatial learning
publication: eNeuro
publication_status: published
publisher: Society of Neuroscience
quality_controlled: '1'
related_material:
record:
- id: '6849'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 'Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR
events to learning'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 5
year: '2018'
...
---
_id: '402'
abstract:
- lang: eng
text: During metastasis, malignant cells escape the primary tumor, intravasate lymphatic
vessels, and reach draining sentinel lymph nodes before they colonize distant
organs via the blood circulation. Although lymph node metastasis in cancer patients
correlates with poor prognosis, evidence is lacking as to whether and how tumor
cells enter the bloodstream via lymph nodes. To investigate this question, we
delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells
into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated
the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without
involvement of the thoracic duct. These results suggest that the lymph node blood
vessels can serve as an exit route for systemic dissemination of cancer cells
in experimental mouse models. Whether this form of tumor cell spreading occurs
in cancer patients remains to be determined.
acknowledged_ssus:
- _id: Bio
acknowledgement: "M.B. was supported by the Cell Communication in Health and Disease
graduate study program of the Austrian Science Fund (FWF) and the Medical University
of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556)
and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic
injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster
and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri
for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging,
the Sixt lab for intellectual input, M. Schunn for help with the design of the in
vivo experiments, F. Langer for technical assistance with the in vivo experiments,
the bioimaging facility of IST Austria for support, and R. Efferl for providing
the CT26 cell line."
article_processing_charge: No
article_type: original
author:
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Helga
full_name: Schachner, Helga
last_name: Schachner
- first_name: Gabriele
full_name: Asfour, Gabriele
last_name: Asfour
- first_name: Zsuzsanna
full_name: Bagó Horváth, Zsuzsanna
last_name: Bagó Horváth
- first_name: Jens
full_name: Stein, Jens
last_name: Stein
- first_name: Pavel
full_name: Uhrin, Pavel
last_name: Uhrin
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
citation:
ama: Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit
routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411.
doi:10.1126/science.aal3662
apa: Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G.,
… Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic
tumor cell dissemination in mice. Science. American Association for the
Advancement of Science. https://doi.org/10.1126/science.aal3662
chicago: Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner,
Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide
Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science.
American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662.
ieee: M. Brown et al., “Lymph node blood vessels provide exit routes for
metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382.
American Association for the Advancement of Science, pp. 1408–1411, 2018.
ista: Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth
Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide
exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382),
1408–1411.
mla: Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic
Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American
Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.
short: M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z.
Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018)
1408–1411.
date_created: 2018-12-11T11:46:16Z
date_published: 2018-03-23T00:00:00Z
date_updated: 2024-03-28T23:30:09Z
day: '23'
department:
- _id: MiSi
doi: 10.1126/science.aal3662
ec_funded: 1
external_id:
isi:
- '000428043600047'
pmid:
- '29567714'
intvolume: ' 359'
isi: 1
issue: '6382'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1126/science.aal3662
month: '03'
oa: 1
oa_version: Published Version
page: 1408 - 1411
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7428'
quality_controlled: '1'
related_material:
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status: public
scopus_import: '1'
status: public
title: Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination
in mice
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 359
year: '2018'
...
---
_id: '395'
abstract:
- lang: eng
text: 'Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. Despite the remarkable number of scientific
breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders
(e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great
challenge. Recent advancements in geno mics, like whole-exome or whole-genome
sequencing, have enabled scientists to identify numerous mutations underlying
neurodevelopmental disorders. Given the few hundred risk genes that were discovered,
the etiological variability and the heterogeneous phenotypic outcomes, the need
for genotype -along with phenotype- based diagnosis of individual patients becomes
a requisite. Driven by this rationale, in a previous study our group described
mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding
for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause
of ASD. Following up on the role of BCAAs, in the study described here we show
that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter
localized mainly at the blood brain barrier (BBB), has an essential role in maintaining
normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial
cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation
and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from
the neural progenitor cell population leads to microcephaly. Interestingly, we
demonstrate that BCAA intracerebroventricular administration ameliorates abnormal
behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients
diagnosed with neurological dis o r ders helped us identify several patients with
autistic traits, microcephaly and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological
syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA
s in human bra in function. Together with r ecent studies (described in chapter
two) that have successfully made the transition into clinical practice, our findings
on the role of B CAAs might have a crucial impact on the development of novel
individualized therapeutic strategies for ASD. '
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
citation:
ama: Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders
. 2018. doi:10.15479/AT:ISTA:th_992
apa: Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum
disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992
chicago: Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum
Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.
ieee: D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders
,” Institute of Science and Technology Austria, 2018.
ista: Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders
. Institute of Science and Technology Austria.
mla: Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum
Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.
short: D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders
, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:46:14Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2023-09-07T12:38:59Z
day: '01'
ddc:
- '570'
- '616'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:th_992
file:
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checksum: 9f5231c96e0ad945040841a8630232da
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T23:30:15Z
embargo_to: open_access
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file_name: 2018_Thesis_Tarlungeanu_source.docx
file_size: 43684035
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content_type: application/pdf
creator: dernst
date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T11:17:16Z
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language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '88'
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7434'
pubrep_id: '992'
related_material:
record:
- id: '1183'
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: 'The branched chain amino acids in autism spectrum disorders '
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '51'
abstract:
- lang: eng
text: Asymmetries have long been known about in the central nervous system. From
gross anatomical differences, such as the presence of the parapineal organ in
only one hemisphere of the developing zebrafish, to more subtle differences in
activity between both hemispheres, as seen in freely roaming animals or human
participants under PET and fMRI imaging analysis. The presence of asymmetries
has been demonstrated to have huge behavioural implications, with their disruption
often leading to the generation of neurological disorders, memory problems, changes
in personality, and in an organism's health and well-being. For my Ph.D. work
I aimed to tackle two important avenues of research. The first being the process
of input-side dependency in the hippocampus, with the goal of finding a key gene
responsible for its development (Gene X). The second project was to do with experience-induced
laterality formation in the hippocampus. Specifically, how laterality in the synapse
density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental
enrichment. Through unilateral tracer injections into the CA3, I was able to selectively
measure the properties of synapses within the CA1 and investigate how they differed
based upon which hemisphere the presynaptic neurone originated. Having found the
existence of a previously unreported reversed (left-isomerism) i.v. mutant, through
morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate
a key gene responsible for the process of left or right determination of inputs
to the CA1 s.r.. This work relates to the previous finding of input-side dependent
asymmetry in the wild-type rodent, where the origin of the projecting neurone
to the CA1 will determine the morphology of a synapse, to a greater degree than
the hemisphere in which the projection terminates. Using left- and right-isomerism
i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like
(Evl) as a potential target for Gene X. In relation to this topic, I also highlight
my work in the recently published paper of how knockout of PirB can lead to a
lack of input-side dependency in the murine hippocampus. For the second question,
I show that the environmental enrichment paradigm will lead to an asymmetry in
the synapse densities in the hippocampus of mice. I also highlight that the nature
of the enrichment is of less consequence than the process of enrichment itself.
I demonstrate that the CA3 region will dramatically alter its projection targets,
in relation to environmental stimulation, with the asymmetry in synaptic density,
caused by enrichment, relying heavily on commissural fibres. I also highlight
the vital importance of input-side dependent asymmetry, as a necessary component
of experience-dependent laterality formation in the CA1 s.r.. However, my results
suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism
also at play. Upon further investigation, I highlight the significant, and highly
important, finding that the changes seen in the CA1 s.r. were predominantly caused
through projections from the left-CA3, with the right-CA3 having less involvement
in this mechanism.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
citation:
ama: 'Case MJ. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. 2018. doi:10.15479/AT:ISTA:th_1032'
apa: 'Case, M. J. (2018). From the left to the right: A tale of asymmetries,
environments, and hippocampal development. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:th_1032'
chicago: 'Case, Matthew J. “From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th_1032.'
ieee: 'M. J. Case, “From the left to the right: A tale of asymmetries, environments,
and hippocampal development,” Institute of Science and Technology Austria, 2018.'
ista: 'Case MJ. 2018. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. Institute of Science and Technology Austria.'
mla: 'Case, Matthew J. From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th_1032.'
short: 'M.J. Case, From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development, Institute of Science and Technology Austria, 2018.'
date_created: 2018-12-11T11:44:22Z
date_published: 2018-06-27T00:00:00Z
date_updated: 2023-09-07T12:39:22Z
day: '27'
ddc:
- '571'
- '576'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:th_1032
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language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '186'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8003'
pubrep_id: '1032'
related_material:
record:
- id: '682'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: 'From the left to the right: A tale of asymmetries, environments, and hippocampal
development'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...