---
_id: '8557'
abstract:
- lang: eng
text: The infiltration of immune cells into tissues underlies the establishment
of tissue resident macrophages, and responses to infections and tumors. Yet the
mechanisms immune cells utilize to negotiate tissue barriers in living organisms
are not well understood, and a role for cortical actin has not been examined.
Here we find that the tissue invasion of Drosophila macrophages, also known as
plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
by the Drosophila member of the fos proto oncogene transcription factor family
(Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
F-actin levels around the entire macrophage surface by increasing mRNA levels
of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
filamin Cheerio which are themselves required for invasion. Cortical F-actin levels
are critical as expressing a dominant active form of Diaphanous, a actin polymerizing
Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo
imaging shows that Dfos is required to enhance the efficiency of the initial phases
of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
in macrophages counteracts the constraint produced by the tension of surrounding
tissues and buffers the mechanical properties of the macrophage nucleus from affecting
tissue entry. We thus identify tuning the cortical actin cytoskeleton through
Dfos as a key process allowing efficient forward movement of an immune cell into
surrounding tissues.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: The Drosophila Genomics
Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner.
B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center
supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for
fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and
the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies,
we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice
Kennedy Shriver National Institute of Child Health and Human Development of the
NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her
generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for
RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
for technical support and assistance with microscopy and FACS analysis. We thank
C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and
T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported
by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie
CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European
Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is
supported by an OEAW, DOC fellowship.'
article_processing_charge: No
author:
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
- first_name: Igor
full_name: Gridchyn, Igor
id: 4B60654C-F248-11E8-B48F-1D18A9856A87
last_name: Gridchyn
orcid: 0000-0002-1807-1929
- first_name: Markus
full_name: Linder, Markus
last_name: Linder
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Maria
full_name: Sibilia, Maria
last_name: Sibilia
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled
by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance.
bioRxiv. doi:10.1101/2020.09.18.301481
apa: Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György,
A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila
Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv.
https://doi.org/10.1101/2020.09.18.301481
chicago: Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi
Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin
Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding
Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481.
ieee: V. Belyaeva et al., “Cortical actin properties controlled by Drosophila
Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv.
.
ista: Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia
M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage
infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481.
mla: Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila
Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv,
doi:10.1101/2020.09.18.301481.
short: V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György,
M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).
corr_author: '1'
date_created: 2020-09-23T09:36:47Z
date_published: 2020-09-18T00:00:00Z
date_updated: 2026-04-27T22:30:44Z
day: '18'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1101/2020.09.18.301481
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.09.18.301481
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage
migration
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '10614'
relation: later_version
status: public
- id: '8983'
relation: dissertation_contains
status: public
status: public
title: Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration
against surrounding tissue resistance
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
OA_place: repository
OA_type: green
_id: '7885'
abstract:
- lang: eng
text: Eukaryotic cells migrate by coupling the intracellular force of the actin
cytoskeleton to the environment. While force coupling is usually mediated by transmembrane
adhesion receptors, especially those of the integrin family, amoeboid cells such
as leukocytes can migrate extremely fast despite very low adhesive forces1. Here
we show that leukocytes cannot only migrate under low adhesion but can also transmit
forces in the complete absence of transmembrane force coupling. When confined
within three-dimensional environments, they use the topographical features of
the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton
follows the texture of the substrate, creating retrograde shear forces that are
sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent
migration are not mutually exclusive, but rather are variants of the same principle
of coupling retrograde actin flow to the environment and thus can potentially
operate interchangeably and simultaneously. As adhesion-free migration is independent
of the chemical composition of the environment, it renders cells completely autonomous
in their locomotive behaviour.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank A. Leithner and J. Renkawitz for discussion and critical
reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic
setups; the Bioimaging Facility of IST Austria for excellent support, as well as
the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan,
L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme.
This work was supported by the European Research Council (ERC StG 281556 and CoG
724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF
to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476).
F.G. received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Juan L
full_name: Aguilera Servin, Juan L
id: 2A67C376-F248-11E8-B48F-1D18A9856A87
last_name: Aguilera Servin
orcid: 0000-0002-2862-8372
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Matthieu
full_name: Piel, Matthieu
last_name: Piel
- first_name: Andrew
full_name: Callan-Jones, Andrew
last_name: Callan-Jones
- first_name: Raphael
full_name: Voituriez, Raphael
last_name: Voituriez
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental
topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z
apa: Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera
Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography.
Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z
chicago: Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan,
Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental
Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z.
ieee: A. Reversat et al., “Cellular locomotion using environmental topography,”
Nature, vol. 582. Springer Nature, pp. 582–585, 2020.
ista: Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL,
de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK.
2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.
mla: Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.”
Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.
short: A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera
Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez,
M.K. Sixt, Nature 582 (2020) 582–585.
date_created: 2020-05-24T22:01:01Z
date_published: 2020-06-25T00:00:00Z
date_updated: 2026-04-27T22:30:54Z
day: '25'
department:
- _id: NanoFab
- _id: Bio
- _id: MiSi
doi: 10.1038/s41586-020-2283-z
ec_funded: 1
external_id:
isi:
- '000532688300008'
pmid:
- '32581372'
intvolume: ' 582'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/793919
month: '06'
oa: 1
oa_version: Preprint
page: 582–585
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/
record:
- id: '14697'
relation: dissertation_contains
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cellular locomotion using environmental topography
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 582
year: '2020'
...
---
_id: '7815'
abstract:
- lang: eng
text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
forms highly organized functional neural circuits. However, the underlying cellular
and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
and eventual production of neurons and glia in the developing neuroepithelium
remains unclear. Methods to trace NSC division patterns and map the lineage of
clonally related cells have advanced dramatically. However, many contemporary
lineage tracing techniques suffer from the lack of cellular resolution of progeny
cell fate, which is essential for deciphering progenitor cell division patterns.
Presented is a protocol using mosaic analysis with double markers (MADM) to perform
in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
cells and visualizes precise division patterns and lineage progression at unprecedented
single cell resolution. MADM-based interchromosomal recombination events during
the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
exact information on the birth dates of clones and their division patterns. Thus,
MADM lineage tracing provides unprecedented qualitative and quantitative optical
readouts of the proliferation mode of stem cell progenitors at the single cell
level. MADM also allows for examination of the mechanisms and functional requirements
of candidate genes in NSC lineage progression. This method is unique in that comparative
analysis of control and mutant subclones can be performed in the same tissue environment
in vivo. Here, the protocol is described in detail, and experimental paradigms
to employ MADM for clonal analysis and lineage tracing in the developing cerebral
cortex are demonstrated. Importantly, this protocol can be adapted to perform
MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
in developing cerebral cortex using mosaic analysis with double markers (MADM).
Journal of Visual Experiments. 2020;(159). doi:10.3791/61147
apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM). Journal of
Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147
chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.
ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM),” Journal
of Visual Experiments, no. 159. MyJove Corporation, 2020.
ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
e61147.
mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal
of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147.
short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
S. Hippenmeyer, Journal of Visual Experiments (2020).
corr_author: '1'
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2026-04-27T22:30:56Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
isi:
- '000546406600043'
pmid:
- '32449730'
file:
- access_level: open_access
checksum: 3154ea7f90b9fb45e084cd1c2770597d
content_type: application/pdf
creator: rbeattie
date_created: 2020-05-11T08:28:38Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7816'
file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf
file_size: 1352186
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
isi: 1
issue: '159'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Journal of Visual Experiments
publication_identifier:
issn:
- 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
record:
- id: '7902'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
analysis with double markers (MADM)
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '6025'
abstract:
- lang: eng
text: Non-canonical Wnt signaling plays a central role for coordinated cell polarization
and directed migration in metazoan development. While spatiotemporally restricted
activation of non-canonical Wnt-signaling drives cell polarization in epithelial
tissues, it remains unclear whether such instructive activity is also critical
for directed mesenchymal cell migration. Here, we developed a light-activated
version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted
activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm
(prechordal plate, ppl) cell migration within the zebrafish gastrula. We found
that Fz7 signaling is required for ppl cell protrusion formation and migration
and that spatiotemporally restricted ectopic activation is capable of redirecting
their migration. Finally, we show that uniform activation of Fz7 signaling in
ppl cells fully rescues defective directed cell migration in fz7 mutant embryos.
Together, our findings reveal that in contrast to the situation in epithelial
cells, non-canonical Wnt signaling functions permissively rather than instructively
in directed mesenchymal cell migration during gastrulation.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
article_number: e42093
article_processing_charge: No
author:
- first_name: Daniel
full_name: Capek, Daniel
id: 31C42484-F248-11E8-B48F-1D18A9856A87
last_name: Capek
orcid: 0000-0001-5199-9940
- first_name: Michael
full_name: Smutny, Michael
id: 3FE6E4E8-F248-11E8-B48F-1D18A9856A87
last_name: Smutny
orcid: 0000-0002-5920-9090
- first_name: Alexandra Madelaine
full_name: Tichy, Alexandra Madelaine
last_name: Tichy
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated
Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm
cell migration. eLife. 2019;8. doi:10.7554/eLife.42093
apa: Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., & Heisenberg,
C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical
wnt signaling in mesendoderm cell migration. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.42093
chicago: Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri,
Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals
a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.”
ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42093.
ieee: D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg,
“Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration,” eLife, vol. 8. eLife Sciences Publications,
2019.
ista: Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019.
Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration. eLife. 8, e42093.
mla: Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role
of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife, vol.
8, e42093, eLife Sciences Publications, 2019, doi:10.7554/eLife.42093.
short: D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg,
ELife 8 (2019).
date_created: 2019-02-17T22:59:22Z
date_published: 2019-02-06T00:00:00Z
date_updated: 2025-04-14T07:46:59Z
day: '06'
ddc:
- '570'
department:
- _id: CaHe
- _id: HaJa
doi: 10.7554/eLife.42093
ec_funded: 1
external_id:
isi:
- '000458025300001'
file:
- access_level: open_access
checksum: 6cb4ca6d4aa96f6f187a5983aa3e660a
content_type: application/pdf
creator: dernst
date_created: 2019-02-18T15:17:21Z
date_updated: 2020-07-14T12:47:17Z
file_id: '6041'
file_name: 2019_elife_Capek.pdf
file_size: 5500707
relation: main_file
file_date_updated: 2020-07-14T12:47:17Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration
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: 8
year: '2019'
...
---
_id: '6087'
abstract:
- lang: eng
text: Cell fate specification by lateral inhibition typically involves contact signaling
through the Delta-Notch signaling pathway. However, whether this is the only signaling
mode mediating lateral inhibition remains unclear. Here we show that in zebrafish
oogenesis, a group of cells within the granulosa cell layer at the oocyte animal
pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei.
One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly
high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically
compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly,
relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear
TAZ accumulation in neighboring cells, eventually leading to MPC re-specification
from these cells. Conversely, MPC specification is defective in taz−/− follicles.
These findings uncover a novel mode of lateral inhibition in cell fate specification
based on mechanical signals controlling TAZ activity.
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: LifeSc
acknowledgement: We thank Roland Dosch, Makoto Furutani-Seiki, Brian Link, Mary Mullins,
and Masazumi Tada for providing transgenic and/or mutant zebrafish lines; Alexandra
Schauer, Shayan Shami-Pour, and the rest of the Heisenberg lab for technical assistance
and feedback on the manuscript; and the Bioimaging, Electron Microscopy, and Zebrafish
facilities of IST Austria for continuous support. This work was supported by an
ERC advanced grant ( MECSPEC to C.-P.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Peng
full_name: Xia, Peng
id: 4AB6C7D0-F248-11E8-B48F-1D18A9856A87
last_name: Xia
orcid: 0000-0002-5419-7756
- first_name: Daniel J
full_name: Gütl, Daniel J
id: 381929CE-F248-11E8-B48F-1D18A9856A87
last_name: Gütl
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. Lateral inhibition in cell specification
mediated by mechanical signals modulating TAZ activity. Cell. 2019;176(6):1379-1392.e14.
doi:10.1016/j.cell.2019.01.019
apa: Xia, P., Gütl, D. J., Zheden, V., & Heisenberg, C.-P. J. (2019). Lateral
inhibition in cell specification mediated by mechanical signals modulating TAZ
activity. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.01.019
chicago: Xia, Peng, Daniel J Gütl, Vanessa Zheden, and Carl-Philipp J Heisenberg.
“Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating
TAZ Activity.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.01.019.
ieee: P. Xia, D. J. Gütl, V. Zheden, and C.-P. J. Heisenberg, “Lateral inhibition
in cell specification mediated by mechanical signals modulating TAZ activity,”
Cell, vol. 176, no. 6. Elsevier, p. 1379–1392.e14, 2019.
ista: Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. 2019. Lateral inhibition in cell
specification mediated by mechanical signals modulating TAZ activity. Cell. 176(6),
1379–1392.e14.
mla: Xia, Peng, et al. “Lateral Inhibition in Cell Specification Mediated by Mechanical
Signals Modulating TAZ Activity.” Cell, vol. 176, no. 6, Elsevier, 2019,
p. 1379–1392.e14, doi:10.1016/j.cell.2019.01.019.
short: P. Xia, D.J. Gütl, V. Zheden, C.-P.J. Heisenberg, Cell 176 (2019) 1379–1392.e14.
date_created: 2019-03-10T22:59:19Z
date_published: 2019-03-07T00:00:00Z
date_updated: 2025-04-14T07:46:59Z
day: '07'
department:
- _id: CaHe
- _id: EM-Fac
doi: 10.1016/j.cell.2019.01.019
ec_funded: 1
external_id:
isi:
- '000460509600013'
pmid:
- '30773315'
intvolume: ' 176'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cell.2019.01.019
month: '03'
oa: 1
oa_version: Published Version
page: 1379-1392.e14
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
publication: Cell
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/in-zebrafish-eggs-most-rapidly-growing-cell-inhibits-its-neighbours-through-mechanical-signals/
scopus_import: '1'
status: public
title: Lateral inhibition in cell specification mediated by mechanical signals modulating
TAZ activity
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 176
year: '2019'
...
---
_id: '7026'
abstract:
- lang: eng
text: Effective design of combination therapies requires understanding the changes
in cell physiology that result from drug interactions. Here, we show that the
genome-wide transcriptional response to combinations of two drugs, measured at
a rigorously controlled growth rate, can predict higher-order antagonism with
a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90%
of the variation in cellular response can be decomposed into three principal components
(PCs) that have clear biological interpretations. We demonstrate that the third
PC captures emergent transcriptional programs that are dependent on both drugs
and can predict antagonism with a third drug targeting the emergent pathway. We
further show that emergent gene expression patterns are most pronounced at a drug
ratio where the drug interaction is strongest, providing a guideline for future
measurements. Our results provide a readily applicable recipe for uncovering emergent
responses in other systems and for higher-order drug combinations. A record of
this paper’s transparent peer review process is included in the Supplemental Information.
acknowledged_ssus:
- _id: LifeSc
article_processing_charge: No
article_type: original
author:
- first_name: Martin
full_name: Lukacisin, Martin
id: 298FFE8C-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisin
orcid: 0000-0001-6549-4177
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Lukacisin M, Bollenbach MT. Emergent gene expression responses to drug combinations
predict higher-order drug interactions. Cell Systems. 2019;9(5):423-433.e1-e3.
doi:10.1016/j.cels.2019.10.004
apa: Lukacisin, M., & Bollenbach, M. T. (2019). Emergent gene expression responses
to drug combinations predict higher-order drug interactions. Cell Systems.
Cell Press. https://doi.org/10.1016/j.cels.2019.10.004
chicago: Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression
Responses to Drug Combinations Predict Higher-Order Drug Interactions.” Cell
Systems. Cell Press, 2019. https://doi.org/10.1016/j.cels.2019.10.004.
ieee: M. Lukacisin and M. T. Bollenbach, “Emergent gene expression responses to
drug combinations predict higher-order drug interactions,” Cell Systems,
vol. 9, no. 5. Cell Press, pp. 423-433.e1-e3, 2019.
ista: Lukacisin M, Bollenbach MT. 2019. Emergent gene expression responses to drug
combinations predict higher-order drug interactions. Cell Systems. 9(5), 423-433.e1-e3.
mla: Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression Responses
to Drug Combinations Predict Higher-Order Drug Interactions.” Cell Systems,
vol. 9, no. 5, Cell Press, 2019, pp. 423-433.e1-e3, doi:10.1016/j.cels.2019.10.004.
short: M. Lukacisin, M.T. Bollenbach, Cell Systems 9 (2019) 423-433.e1-e3.
date_created: 2019-11-15T10:51:42Z
date_published: 2019-11-27T00:00:00Z
date_updated: 2025-04-15T08:09:37Z
day: '27'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1016/j.cels.2019.10.004
external_id:
isi:
- '000499495400003'
file:
- access_level: open_access
checksum: 7a11d6c2f9523d65b049512d61733178
content_type: application/pdf
creator: dernst
date_created: 2019-11-15T10:57:42Z
date_updated: 2020-07-14T12:47:48Z
file_id: '7027'
file_name: 2019_CellSystems_Lukacisin.pdf
file_size: 4238460
relation: main_file
file_date_updated: 2020-07-14T12:47:48Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '5'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 423-433.e1-e3
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
grant_number: RGP0042/2013
name: Revealing the fundamental limits of cell growth
publication: Cell Systems
publication_identifier:
issn:
- 2405-4712
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Emergent gene expression responses to drug combinations predict higher-order
drug interactions
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: 9
year: '2019'
...
---
_id: '6897'
abstract:
- lang: eng
text: The apical hook is a transiently formed structure that plays a protective
role when the germinating seedling penetrates through the soil towards the surface.
Crucial for proper bending is the local auxin maxima, which defines the concave
(inner) side of the hook curvature. As no sign of asymmetric auxin distribution
has been reported in embryonic hypocotyls prior to hook formation, the question
of how auxin asymmetry is established in the early phases of seedling germination
remains largely unanswered. Here, we analyzed the auxin distribution and expression
of PIN auxin efflux carriers from early phases of germination, and show that bending
of the root in response to gravity is the crucial initial cue that governs the
hypocotyl bending required for apical hook formation. Importantly, polar auxin
transport machinery is established gradually after germination starts as a result
of tight root-hypocotyl interaction and a proper balance between abscisic acid
and gibberellins.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: "We thank Jiri Friml and Phillip Brewer for inspiring discussion
and for help in preparing the manuscript. This research was supported by the Scientific
Service Units (SSU) of IST-Austria through resources provided by the Bioimaging
Facility\r\n(BIF), the Life Science Facility (LSF).\r\nThis work was supported by
grants from the European Research Council (Starting Independent Research Grant ERC-2007-Stg-
207362-HCPO to E.B.). J.P. and M.S. received funds from European Regional Development
Fund-Project ‘Centre for Experimental Plant Biology’ (No. CZ.02.1.01/0.0/0.0/16_019/0000738)."
article_number: dev175919
article_processing_charge: No
article_type: original
author:
- first_name: Qiang
full_name: Zhu, Qiang
id: 40A4B9E6-F248-11E8-B48F-1D18A9856A87
last_name: Zhu
- first_name: Marçal
full_name: Gallemi, Marçal
id: 460C6802-F248-11E8-B48F-1D18A9856A87
last_name: Gallemi
orcid: 0000-0003-4675-6893
- first_name: Jiří
full_name: Pospíšil, Jiří
last_name: Pospíšil
- first_name: Petra
full_name: Žádníková, Petra
last_name: Žádníková
- first_name: Miroslav
full_name: Strnad, Miroslav
last_name: Strnad
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. Root gravity
response module guides differential growth determining both root bending and apical
hook formation in Arabidopsis. Development. 2019;146(17). doi:10.1242/dev.175919
apa: Zhu, Q., Gallemi, M., Pospíšil, J., Žádníková, P., Strnad, M., & Benková,
E. (2019). Root gravity response module guides differential growth determining
both root bending and apical hook formation in Arabidopsis. Development.
The Company of Biologists. https://doi.org/10.1242/dev.175919
chicago: Zhu, Qiang, Marçal Gallemi, Jiří Pospíšil, Petra Žádníková, Miroslav Strnad,
and Eva Benková. “Root Gravity Response Module Guides Differential Growth Determining
Both Root Bending and Apical Hook Formation in Arabidopsis.” Development.
The Company of Biologists, 2019. https://doi.org/10.1242/dev.175919.
ieee: Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, and E. Benková,
“Root gravity response module guides differential growth determining both root
bending and apical hook formation in Arabidopsis,” Development, vol. 146,
no. 17. The Company of Biologists, 2019.
ista: Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. 2019. Root
gravity response module guides differential growth determining both root bending
and apical hook formation in Arabidopsis. Development. 146(17), dev175919.
mla: Zhu, Qiang, et al. “Root Gravity Response Module Guides Differential Growth
Determining Both Root Bending and Apical Hook Formation in Arabidopsis.” Development,
vol. 146, no. 17, dev175919, The Company of Biologists, 2019, doi:10.1242/dev.175919.
short: Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, E. Benková, Development
146 (2019).
date_created: 2019-09-22T22:00:36Z
date_published: 2019-09-12T00:00:00Z
date_updated: 2026-04-03T09:45:02Z
day: '12'
department:
- _id: EvBe
doi: 10.1242/dev.175919
ec_funded: 1
external_id:
isi:
- '000486297400011'
pmid:
- '31391194'
intvolume: ' 146'
isi: 1
issue: '17'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1242/dev.175919
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 253FCA6A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '207362'
name: Hormonal cross-talk in plant organogenesis
publication: Development
publication_identifier:
eissn:
- 1477-9129
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Root gravity response module guides differential growth determining both root
bending and apical hook formation in Arabidopsis
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 146
year: '2019'
...
---
_id: '7197'
abstract:
- lang: eng
text: During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like
structure at the center of the cell. This Z-ring not only organizes the division
machinery, but treadmilling of FtsZ filaments was also found to play a key role
in distributing proteins at the division site. What regulates the architecture,
dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated
proteins are known to play an important role. Here, using an in vitro reconstitution
approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling
and filament organization into large-scale patterns. Using high-resolution fluorescence
microscopy and quantitative image analysis, we found that ZapA cooperatively increases
the spatial order of the filament network, but binds only transiently to FtsZ
filaments and has no effect on filament length and treadmilling velocity. Together,
our data provides a model for how FtsZ-associated proteins can increase the precision
and stability of the bacterial cell division machinery in a switch-like manner.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
article_number: '5744'
article_processing_charge: No
article_type: original
author:
- first_name: Paulo R
full_name: Dos Santos Caldas, Paulo R
id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87
last_name: Dos Santos Caldas
orcid: 0000-0001-6730-4461
- first_name: Maria D
full_name: Lopez Pelegrin, Maria D
id: 319AA9CE-F248-11E8-B48F-1D18A9856A87
last_name: Lopez Pelegrin
- first_name: Daniel J. G.
full_name: Pearce, Daniel J. G.
last_name: Pearce
- first_name: Nazmi B
full_name: Budanur, Nazmi B
id: 3EA1010E-F248-11E8-B48F-1D18A9856A87
last_name: Budanur
orcid: 0000-0003-0423-5010
- first_name: Jan
full_name: Brugués, Jan
last_name: Brugués
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
citation:
ama: Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J,
Loose M. Cooperative ordering of treadmilling filaments in cytoskeletal networks
of FtsZ and its crosslinker ZapA. Nature Communications. 2019;10. doi:10.1038/s41467-019-13702-4
apa: Dos Santos Caldas, P. R., Lopez Pelegrin, M. D., Pearce, D. J. G., Budanur,
N. B., Brugués, J., & Loose, M. (2019). Cooperative ordering of treadmilling
filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. Nature
Communications. Springer Nature. https://doi.org/10.1038/s41467-019-13702-4
chicago: Dos Santos Caldas, Paulo R, Maria D Lopez Pelegrin, Daniel J. G. Pearce,
Nazmi B Budanur, Jan Brugués, and Martin Loose. “Cooperative Ordering of Treadmilling
Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” Nature
Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-13702-4.
ieee: P. R. Dos Santos Caldas, M. D. Lopez Pelegrin, D. J. G. Pearce, N. B. Budanur,
J. Brugués, and M. Loose, “Cooperative ordering of treadmilling filaments in cytoskeletal
networks of FtsZ and its crosslinker ZapA,” Nature Communications, vol.
10. Springer Nature, 2019.
ista: Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J,
Loose M. 2019. Cooperative ordering of treadmilling filaments in cytoskeletal
networks of FtsZ and its crosslinker ZapA. Nature Communications. 10, 5744.
mla: Dos Santos Caldas, Paulo R., et al. “Cooperative Ordering of Treadmilling Filaments
in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” Nature Communications,
vol. 10, 5744, Springer Nature, 2019, doi:10.1038/s41467-019-13702-4.
short: P.R. Dos Santos Caldas, M.D. Lopez Pelegrin, D.J.G. Pearce, N.B. Budanur,
J. Brugués, M. Loose, Nature Communications 10 (2019).
corr_author: '1'
date_created: 2019-12-20T12:22:57Z
date_published: 2019-12-17T00:00:00Z
date_updated: 2026-04-08T07:26:30Z
day: '17'
ddc:
- '570'
department:
- _id: MaLo
- _id: BjHo
doi: 10.1038/s41467-019-13702-4
ec_funded: 1
external_id:
isi:
- '000503009300001'
file:
- access_level: open_access
checksum: a1b44b427ba341383197790d0e8789fa
content_type: application/pdf
creator: dernst
date_created: 2019-12-23T07:34:56Z
date_updated: 2020-07-14T12:47:53Z
file_id: '7208'
file_name: 2019_NatureComm_Caldas.pdf
file_size: 8488733
relation: main_file
file_date_updated: 2020-07-14T12:47:53Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '679239'
name: Self-Organization of the Bacterial Cell
- _id: 260D98C8-B435-11E9-9278-68D0E5697425
name: Reconstitution of Bacterial Cell Division Using Purified Components
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8358'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cooperative ordering of treadmilling filaments in cytoskeletal networks of
FtsZ and its crosslinker ZapA
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: 10
year: '2019'
...
---
OA_place: publisher
_id: '7172'
abstract:
- lang: eng
text: "The development and growth of Arabidopsis thaliana is regulated by a combination
of genetic programing and also by the environmental influences. An important role
in these processes play the phytohormones and among them, auxin is crucial as
it controls many important functions. It is transported through the whole plant
body by creating local and temporal concentration maxima and minima, which have
an impact on the cell status, tissue and organ identity. Auxin has the property
to undergo a directional and finely regulated cell-to-cell transport, which is
enabled by the transport proteins, localized on the plasma membrane. An important
role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar
subcellular localization and determine the directionality of the auxin transport.
During the last years, there were significant advances in understanding how the
trafficking molecular machineries function, including studies on molecular interactions,
function, subcellular localization and intracellular distribution. However, there
is still a lack of detailed characterization on the steps of endocytosis, exocytosis,
endocytic recycling and degradation. Due to this fact, I focused on the identification
of novel trafficking factors and better characterization of the intracellular
trafficking pathways. My PhD thesis consists of an introductory chapter, three
experimental chapters, a chapter containing general discussion, conclusions and
perspectives and also an appendix chapter with published collaborative papers.\r\nThe
first chapter is separated in two different parts: I start by a general introduction
to auxin biology and then I introduce the trafficking pathways in the model plant
Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar
targeting and also the roles of the phytohormone strigolactone.\r\nThe second
chapter includes the characterization of bar1/sacsin mutant, which was identified
in a forward genetic screen for novel trafficking components in Arabidopsis thaliana,
where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and
by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to
study trafficking processes, we identified a novel factor, which is mediating
the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously
uncharacterized gene, encoding a very big protein that we, based on its homologies,
called SACSIN with domains suggesting roles as a molecular chaperon or as a component
of the ubiquitin-proteasome system. Our physiology and imaging studies revealed
that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF
inhibition.\r\nThe third chapter includes six subchapters, where I focus on the
role of the phytohormone strigolactone, which interferes with auxin feedback on
PIN internalization. Strigolactone moderates the polar auxin transport by increasing
the internalization of the PIN auxin efflux carriers, which reduces the canalization
related growth responses. In addition, I also studied the role of phosphorylation
in the strigolactone regulation of auxin feedback on PIN internalization. In this
chapter I also present my results on the MAX2-dependence of strigolactone-mediated
root growth inhibition and I also share my results on the auxin metabolomics profiling
after application of GR24.\r\nIn the fourth chapter I studied the effect of two
small molecules ES-9 and ES9-17, which were identified from a collection of small
molecules with the property to impair the clathrin-mediated endocytosis.\r\nIn
the fifth chapter, I discuss all my observations and experimental findings and
suggest alternative hypothesis to interpret my results.\r\nIn the appendix there
are three collaborative published projects. In the first, I participated in the
characterization of the role of ES9 as a small molecule, which is inhibitor of
clathrin- mediated endocytosis in different model organisms. In the second paper,
I contributed to the characterization of another small molecule ES9-17, which
is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis
not only in plant cells, but also in mammalian HeLa cells. Last but not least,
I also attach another paper, where I tried to establish the grafting method as
a technique in our lab to study canalization related processes."
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Mina K
full_name: Vasileva, Mina K
id: 3407EB18-F248-11E8-B48F-1D18A9856A87
last_name: Vasileva
citation:
ama: Vasileva MK. Molecular mechanisms of endomembrane trafficking in Arabidopsis
thaliana. 2019. doi:10.15479/AT:ISTA:7172
apa: Vasileva, M. K. (2019). Molecular mechanisms of endomembrane trafficking
in Arabidopsis thaliana. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7172
chicago: Vasileva, Mina K. “Molecular Mechanisms of Endomembrane Trafficking in
Arabidopsis Thaliana.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7172.
ieee: M. K. Vasileva, “Molecular mechanisms of endomembrane trafficking in Arabidopsis
thaliana,” Institute of Science and Technology Austria, 2019.
ista: Vasileva MK. 2019. Molecular mechanisms of endomembrane trafficking in Arabidopsis
thaliana. Institute of Science and Technology Austria.
mla: Vasileva, Mina K. Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis
Thaliana. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7172.
short: M.K. Vasileva, Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis
Thaliana, Institute of Science and Technology Austria, 2019.
corr_author: '1'
date_created: 2019-12-11T21:24:39Z
date_published: 2019-12-12T00:00:00Z
date_updated: 2026-04-08T13:54:45Z
day: '12'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: JiFr
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publisher: Institute of Science and Technology Austria
related_material:
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status: public
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relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
title: Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...
---
OA_place: publisher
_id: '7186'
abstract:
- lang: eng
text: "Tissue morphogenesis in developmental or physiological processes is regulated
by molecular\r\nand mechanical signals. While the molecular signaling cascades
are increasingly well\r\ndescribed, the mechanical signals affecting tissue shape
changes have only recently been\r\nstudied in greater detail. To gain more insight
into the mechanochemical and biophysical\r\nbasis of an epithelial spreading process
(epiboly) in early zebrafish development, we studied\r\ncell-cell junction formation
and actomyosin network dynamics at the boundary between\r\nsurface layer epithelial
cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,\r\nthe
cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the
end of\r\ngastrulation. It has been previously shown that an actomyosin ring residing
within the YSL\r\npulls on the EVL tissue through a cable-constriction and a flow-friction
motor, thereby\r\ndragging the tissue vegetal wards. Pulling forces are likely
transmitted from the YSL\r\nactomyosin ring to EVL cells; however, the nature
and formation of the junctional structure\r\nmediating this process has not been
well described so far. Therefore, our main aim was to\r\ndetermine the nature,
dynamics and potential function of the EVL-YSL junction during this\r\nepithelial
tissue spreading. Specifically, we show that the EVL-YSL junction is a\r\nmechanosensitive
structure, predominantly made of tight junction (TJ) proteins. The process\r\nof
TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated\r\nZonula
Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly,
we\r\ncould demonstrate that ZO-1 is present in a non-junctional pool on the surface
of the yolk\r\ncell, and ZO-1 undergoes a phase separation process that likely
renders the protein\r\nresponsive to flows. These flows are directed towards the
junction and mediate proper\r\ntension-dependent recruitment of ZO-1. Upon reaching
the EVL-YSL junction ZO-1 gets\r\nincorporated into the junctional pool mediated
through its direct actin-binding domain.\r\nWhen the non-junctional pool and/or
ZO-1 direct actin binding is absent, TJs fail in their\r\nproper mechanosensitive
responses resulting in slower tissue spreading. We could further\r\ndemonstrate
that depletion of ZO proteins within the YSL results in diminished actomyosin\r\nring
formation. This suggests that a mechanochemical feedback loop is at work during\r\nzebrafish
epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin\r\ncontractility
and flows positively influence ZO-1 junctional recruitment. Finally, such a\r\nmesoscale
polarization process mediated through the flow of phase-separated protein\r\nclusters
might have implications for other processes such as immunological synapse\r\nformation,
C. elegans zygote polarization and wound healing."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: EM-Fac
- _id: SSU
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Cornelia
full_name: Schwayer, Cornelia
id: 3436488C-F248-11E8-B48F-1D18A9856A87
last_name: Schwayer
orcid: 0000-0001-5130-2226
citation:
ama: Schwayer C. Mechanosensation of tight junctions depends on ZO-1 phase separation
and flow. 2019. doi:10.15479/AT:ISTA:7186
apa: Schwayer, C. (2019). Mechanosensation of tight junctions depends on ZO-1
phase separation and flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7186
chicago: Schwayer, Cornelia. “Mechanosensation of Tight Junctions Depends on ZO-1
Phase Separation and Flow.” Institute of Science and Technology Austria, 2019.
https://doi.org/10.15479/AT:ISTA:7186.
ieee: C. Schwayer, “Mechanosensation of tight junctions depends on ZO-1 phase separation
and flow,” Institute of Science and Technology Austria, 2019.
ista: Schwayer C. 2019. Mechanosensation of tight junctions depends on ZO-1 phase
separation and flow. Institute of Science and Technology Austria.
mla: Schwayer, Cornelia. Mechanosensation of Tight Junctions Depends on ZO-1
Phase Separation and Flow. Institute of Science and Technology Austria, 2019,
doi:10.15479/AT:ISTA:7186.
short: C. Schwayer, Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation
and Flow, Institute of Science and Technology Austria, 2019.
corr_author: '1'
date_created: 2019-12-16T14:26:14Z
date_published: 2019-12-16T00:00:00Z
date_updated: 2026-04-08T13:55:29Z
day: '16'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: CaHe
doi: 10.15479/AT:ISTA:7186
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date_updated: 2020-07-14T12:47:52Z
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page: '107'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7001'
relation: part_of_dissertation
status: public
- id: '1096'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
title: Mechanosensation of tight junctions depends on ZO-1 phase separation and flow
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...
---
_id: '6392'
abstract:
- lang: eng
text: "The regulation of gene expression is one of the most fundamental processes
in living systems. In recent years, thanks to advances in sequencing technology
and automation, it has become possible to study gene expression quantitatively,
genome-wide and in high-throughput. This leads to the possibility of exploring
changes in gene expression in the context of many external perturbations and their
combinations, and thus of characterising the basic principles governing gene regulation.
In this thesis, I present quantitative experimental approaches to studying transcriptional
and protein level changes in response to combinatorial drug treatment, as well
as a theoretical data-driven approach to analysing thermodynamic principles guiding
transcription of protein coding genes. \r\nIn the first part of this work, I
present a novel methodological framework for quantifying gene expression changes
in drug combinations, termed isogrowth profiling. External perturbations through
small molecule drugs influence the growth rate of the cell, leading to wide-ranging
changes in cellular physiology and gene expression. This confounds the gene expression
changes specifically elicited by the particular drug. Combinatorial perturbations,
owing to the increased stress they exert, influence the growth rate even more
strongly and hence suffer the convolution problem to a greater extent when measuring
gene expression changes. Isogrowth profiling is a way to experimentally abstract
non-specific, growth rate related changes, by performing the measurement using
varying ratios of two drugs at such concentrations that the overall inhibition
rate is constant. Using a robotic setup for automated high-throughput re-dilution
culture of Saccharomyces cerevisiae, the budding yeast, I investigate all pairwise
interactions of four small molecule drugs through sequencing RNA along a growth
isobole. Through principal component analysis, I demonstrate here that isogrowth
profiling can uncover drug-specific as well as drug-interaction-specific gene
expression changes. I show that drug-interaction-specific gene expression changes
can be used for prediction of higher-order drug interactions. I propose a simplified
generalised framework of isogrowth profiling, with few measurements needed for
each drug pair, enabling the broad application of isogrowth profiling to high-throughput
screening of inhibitors of cellular growth and beyond. Such high-throughput screenings
of gene expression changes specific to pairwise drug interactions will be instrumental
for predicting the higher-order interactions of the drugs.\r\n\r\nIn the second
part of this work, I extend isogrowth profiling to single-cell measurements of
gene expression, characterising population heterogeneity in the budding yeast
in response to combinatorial drug perturbation while controlling for non-specific
growth rate effects. Through flow cytometry of strains with protein products fused
to green fluorescent protein, I discover multiple proteins with bi-modally distributed
expression levels in the population in response to drug treatment. I characterize
more closely the effect of an ionic stressor, lithium chloride, and find that
it inhibits the splicing of mRNA, most strongly affecting ribosomal protein transcripts
and leading to a bi-stable behaviour of a small ribosomal subunit protein Rps22B.
Time-lapse microscopy of a microfluidic culture system revealed that the induced
Rps22B heterogeneity leads to preferential survival of Rps22B-low cells after
long starvation, but to preferential proliferation of Rps22B-high cells after
short starvation. Overall, this suggests that yeast cells might use splicing of
ribosomal genes for bet-hedging in fluctuating environments. I give specific examples
of how further exploration of cellular heterogeneity in yeast in response to external
perturbation has the potential to reveal yet-undiscovered gene regulation circuitry.\r\n\r\nIn
the last part of this thesis, a re-analysis of a published sequencing dataset
of nascent elongating transcripts is used to characterise the thermodynamic constraints
for RNA polymerase II (RNAP) elongation. Population-level data on RNAP position
throughout the transcribed genome with single nucleotide resolution are used to
infer the sequence specific thermodynamic determinants of RNAP pausing and backtracking.
This analysis reveals that the basepairing strength of the eight nucleotide-long
RNA:DNA duplex relative to the basepairing strength of the same sequence when
in DNA:DNA duplex, and the change in this quantity during RNA polymerase movement,
is the key determinant of RNAP pausing. This is true for RNAP pausing while elongating,
but also of RNAP pausing while backtracking and of the backtracking length. The
quantitative dependence of RNAP pausing on basepairing energetics is used to infer
the increase in pausing due to transcriptional mismatches, leading to a hypothesis
that pervasive RNA polymerase II pausing is due to basepairing energetics, as
an evolutionary cost for increased RNA polymerase II fidelity.\r\n\r\nThis work
advances our understanding of the general principles governing gene expression,
with the goal of making computational predictions of single-cell gene expression
responses to combinatorial perturbations based on the individual perturbations
possible. This ability would substantially facilitate the design of drug combination
treatments and, in the long term, lead to our increased ability to more generally
design targeted manipulations to any biological system. "
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
- _id: Bio
alternative_title:
- IST Austria Thesis
author:
- first_name: Martin
full_name: Lukacisin, Martin
id: 298FFE8C-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisin
orcid: 0000-0001-6549-4177
citation:
ama: Lukacisin M. Quantitative investigation of gene expression principles through
combinatorial drug perturbation and theory. 2019. doi:10.15479/AT:ISTA:6392
apa: Lukacisin, M. (2019). Quantitative investigation of gene expression principles
through combinatorial drug perturbation and theory. IST Austria. https://doi.org/10.15479/AT:ISTA:6392
chicago: Lukacisin, Martin. “Quantitative Investigation of Gene Expression Principles
through Combinatorial Drug Perturbation and Theory.” IST Austria, 2019. https://doi.org/10.15479/AT:ISTA:6392.
ieee: M. Lukacisin, “Quantitative investigation of gene expression principles through
combinatorial drug perturbation and theory,” IST Austria, 2019.
ista: Lukacisin M. 2019. Quantitative investigation of gene expression principles
through combinatorial drug perturbation and theory. IST Austria.
mla: Lukacisin, Martin. Quantitative Investigation of Gene Expression Principles
through Combinatorial Drug Perturbation and Theory. IST Austria, 2019, doi:10.15479/AT:ISTA:6392.
short: M. Lukacisin, Quantitative Investigation of Gene Expression Principles through
Combinatorial Drug Perturbation and Theory, IST Austria, 2019.
date_created: 2019-05-09T19:53:00Z
date_published: 2019-05-09T00:00:00Z
date_updated: 2025-07-10T11:49:51Z
day: '09'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.15479/AT:ISTA:6392
extern: '1'
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publication_identifier:
isbn:
- 978-3-99078-001-5
issn:
- 2663-337X
publication_status: published
publisher: IST Austria
related_material:
record:
- id: '1029'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: Quantitative investigation of gene expression principles through combinatorial
drug perturbation and theory
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
OA_place: publisher
_id: '6435'
abstract:
- lang: eng
text: "Social insect colonies tend to have numerous members which function together
like a single organism in such harmony that the term ``super-organism'' is often
used. In this analogy the reproductive caste is analogous to the primordial germ\r\ncells
of a metazoan, while the sterile worker caste corresponds to somatic cells. The
worker castes, like tissues, are\r\nin charge of all functions of a living being,
besides reproduction. The establishment of new super-organismal units\r\n(i.e.
new colonies) is accomplished by the co-dependent castes. The term oftentimes
goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation,
nutrient regulation and gas exchange of a social insect colony. Furthermore, we
assert that the super-organism has an immune system, and benefits from ``social
immunity''.\r\n\r\nSocial immunity was first summoned by evolutionary biologists
to resolve the apparent discrepancy between the expected high frequency of disease
outbreak amongst numerous, closely related tightly-interacting hosts, living in
stable and microbially-rich environments, against the exceptionally scarce epidemic
accounts in natural populations. Social\r\nimmunity comprises a multi-layer assembly
of behaviours which have evolved to effectively keep the pathogenic enemies of
a colony at bay. The field of social immunity has drawn interest, as it becomes
increasingly urgent to stop\r\nthe collapse of pollinator species and curb the
growth of invasive pests. In the past decade, several mechanisms of\r\nsocial
immune responses have been dissected, but many more questions remain open.\r\n\r\nI
present my work in two experimental chapters. In the first, I use invasive garden
ants (*Lasius neglectus*) to study how pathogen load and its distribution among
nestmates affect the grooming response of the group. Any given group of ants will
carry out the same total grooming work, but will direct their grooming effort
towards individuals\r\ncarrying a relatively higher spore load. Contrary to expectation,
the highest risk of transmission does not stem from grooming highly contaminated
ants, but instead, we suggest that the grooming response likely minimizes spore
loss to the environment, reducing contamination from inadvertent pickup from the
substrate.\r\n\r\nThe second is a comparative developmental approach. I follow
black garden ant queens (*Lasius niger*) and their colonies from mating flight,
through hibernation for a year. Colonies which grow fast from the start, have
a lower chance of survival through hibernation, and those which survive grow at
a lower pace later. This is true for colonies of naive\r\nand challenged queens.
Early pathogen exposure of the queens changes colony dynamics in an unexpected
way: colonies from exposed queens are more likely to grow slowly and recover in
numbers only after they survive hibernation.\r\n\r\nIn addition to the two experimental
chapters, this thesis includes a co-authored published review on organisational\r\nimmunity,
where we enlist the experimental evidence and theoretical framework on which this
hypothesis is built,\r\nidentify the caveats and underline how the field is ripe
to overcome them. In a final chapter, I describe my part in\r\ntwo collaborative
efforts, one to develop an image-based tracker, and the second to develop a classifier
for ant\r\nbehaviour."
acknowledged_ssus:
- _id: Bio
- _id: ScienComp
- _id: M-Shop
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Barbara E
full_name: Casillas Perez, Barbara E
id: 351ED2AA-F248-11E8-B48F-1D18A9856A87
last_name: Casillas Perez
citation:
ama: Casillas Perez BE. Collective defenses of garden ants against a fungal pathogen.
2019. doi:10.15479/AT:ISTA:6435
apa: Casillas Perez, B. E. (2019). Collective defenses of garden ants against
a fungal pathogen. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6435
chicago: Casillas Perez, Barbara E. “Collective Defenses of Garden Ants against
a Fungal Pathogen.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6435.
ieee: B. E. Casillas Perez, “Collective defenses of garden ants against a fungal
pathogen,” Institute of Science and Technology Austria, 2019.
ista: Casillas Perez BE. 2019. Collective defenses of garden ants against a fungal
pathogen. Institute of Science and Technology Austria.
mla: Casillas Perez, Barbara E. Collective Defenses of Garden Ants against a
Fungal Pathogen. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6435.
short: B.E. Casillas Perez, Collective Defenses of Garden Ants against a Fungal
Pathogen, Institute of Science and Technology Austria, 2019.
corr_author: '1'
date_created: 2019-05-13T08:58:35Z
date_published: 2019-05-07T00:00:00Z
date_updated: 2026-04-08T14:02:12Z
day: '07'
ddc:
- '570'
- '006'
- '578'
- '592'
degree_awarded: PhD
department:
- _id: SyCr
doi: 10.15479/AT:ISTA:6435
ec_funded: 1
file:
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checksum: 6daf2d2086111aa8fd3fbc919a3e2833
content_type: application/pdf
creator: casillas
date_created: 2019-05-13T09:16:20Z
date_updated: 2021-02-11T11:17:15Z
embargo: 2020-05-08
file_id: '6438'
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file_size: 3895187
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content_type: application/zip
creator: casillas
date_created: 2019-05-13T09:16:20Z
date_updated: 2020-07-14T12:47:30Z
embargo_to: open_access
file_id: '6439'
file_name: tesisDoctoradoBC.zip
file_size: 7365118
relation: source_file
file_date_updated: 2021-02-11T11:17:15Z
has_accepted_license: '1'
keyword:
- Social Immunity
- Sanitary care
- Social Insects
- Organisational Immunity
- Colony development
- Multi-target tracking
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '183'
project:
- _id: 2649B4DE-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771402'
name: Epidemics in ant societies on a chip
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1999'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sylvia M
full_name: Cremer, Sylvia M
id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87
last_name: Cremer
orcid: 0000-0002-2193-3868
title: Collective defenses of garden ants against a fungal pathogen
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...
---
_id: '6187'
abstract:
- lang: eng
text: Aberrant display of the truncated core1 O-glycan T-antigen is a common feature
of human cancer cells that correlates with metastasis. Here we show that T-antigen
in Drosophila melanogaster macrophages is involved in their developmentally programmed
tissue invasion. Higher macrophage T-antigen levels require an atypical major
facilitator superfamily (MFS) member that we named Minerva which enables macrophage
dissemination and invasion. We characterize for the first time the T and Tn glycoform
O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva
increases the presence of T-antigen on proteins in pathways previously linked
to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required
for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the
minerva mutant’s migration and T-antigen glycosylation defects. We thus identify
a key conserved regulator that orchestrates O-glycosylation on a protein subset
to activate a program governing migration steps important for both development
and cancer metastasis.
acknowledged_ssus:
- _id: LifeSc
article_number: e41801
article_processing_charge: No
author:
- first_name: Katarina
full_name: Valosková, Katarina
id: 46F146FC-F248-11E8-B48F-1D18A9856A87
last_name: Valosková
orcid: 0000-0002-7926-0221
- first_name: Julia
full_name: Biebl, Julia
id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
last_name: Biebl
- first_name: Marko
full_name: Roblek, Marko
id: 3047D808-F248-11E8-B48F-1D18A9856A87
last_name: Roblek
orcid: 0000-0001-9588-1389
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Michaela
full_name: Misova, Michaela
id: 495A3C32-F248-11E8-B48F-1D18A9856A87
last_name: Misova
orcid: 0000-0003-2427-6856
- first_name: Aparna
full_name: Ratheesh, Aparna
id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
last_name: Ratheesh
orcid: 0000-0001-7190-0776
- first_name: Patricia
full_name: Dos Reis Rodrigues, Patricia
id: 26E95904-5160-11E9-9C0B-C5B0DC97E90F
last_name: Dos Reis Rodrigues
orcid: 0000-0003-1681-508X
- first_name: Katerina
full_name: Shkarina, Katerina
last_name: Shkarina
- first_name: Ida Signe Bohse
full_name: Larsen, Ida Signe Bohse
last_name: Larsen
- first_name: Sergey Y
full_name: Vakhrushev, Sergey Y
last_name: Vakhrushev
- first_name: Henrik
full_name: Clausen, Henrik
last_name: Clausen
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily
member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.
eLife. 2019;8. doi:10.7554/elife.41801
apa: Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M.,
… Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates
a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife
Sciences Publications. https://doi.org/10.7554/elife.41801
chicago: Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila
György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator
Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage
Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801.
ieee: K. Valosková et al., “A conserved major facilitator superfamily member
orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife,
vol. 8. eLife Sciences Publications, 2019.
ista: Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh
A, Dos Reis Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus
DE. 2019. A conserved major facilitator superfamily member orchestrates a subset
of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801.
mla: Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member
Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife,
vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801.
short: K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A.
Ratheesh, P. Dos Reis Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev,
H. Clausen, D.E. Siekhaus, ELife 8 (2019).
date_created: 2019-03-28T13:37:45Z
date_published: 2019-03-26T00:00:00Z
date_updated: 2026-04-27T22:30:48Z
day: '26'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.7554/elife.41801
ec_funded: 1
external_id:
isi:
- '000462530200001'
file:
- access_level: open_access
checksum: cc0d1a512559d52e7e7cb0e9b9854b40
content_type: application/pdf
creator: dernst
date_created: 2019-03-28T14:00:41Z
date_updated: 2020-07-14T12:47:23Z
file_id: '6188'
file_name: 2019_eLife_Valoskova.pdf
file_size: 4496017
relation: main_file
file_date_updated: 2020-07-14T12:47:23Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
grant_number: '24283'
name: Examination of the role of a MFS transporter in the migration of Drosophila
immune cells
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
- _id: 25388084-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '329540'
name: 'Breaking barriers: Investigating the junctional and mechanobiological changes
underlying the ability of Drosophila immune cells to invade an epithelium'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/
record:
- id: '6530'
relation: dissertation_contains
- id: '8983'
relation: dissertation_contains
status: public
- id: '6546'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation
to aid macrophage tissue invasion
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 8
year: '2019'
...
---
_id: '544'
abstract:
- lang: eng
text: Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes,
are essential for immune responses, but also play key roles from early development
to death through their interactions with other cell types. They regulate homeostasis
and signaling during development, stem cell proliferation, metabolism, cancer,
wound responses and aging, displaying intriguing molecular and functional conservation
with vertebrate macrophages. Given the relative ease of genetics in Drosophila
compared to vertebrates, tools permitting visualization and genetic manipulation
of plasmatocytes and surrounding tissues independently at all stages would greatly
aid in fully understanding these processes, but are lacking. Here we describe
a comprehensive set of transgenic lines that allow this. These include extremely
brightly fluorescing mCherry-based lines that allow GAL4-independent visualization
of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8
through adulthood in both live and fixed samples even as heterozygotes, greatly
facilitating screening. These lines allow live visualization and tracking of embryonic
plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing
with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes
and inner tissues can be seen in live or fixed embryos, larvae and adults. They
permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout
life. To facilitate genetic analysis of reciprocal signaling, we have also made
a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers
allows independent genetic manipulation of both plasmatocytes and surrounding
tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes,
both of which function from the early embryo to the adult.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: ' A. Ratheesh also by Marie Curie IIF GA-2012-32950BB:DICJI, Marko
Roblek by the provincial government of Lower Austria, K. Valoskova and S. Wachner
by DOC Fellowships from the Austrian Academy of Sciences, '
article_processing_charge: No
author:
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Marko
full_name: Roblek, Marko
id: 3047D808-F248-11E8-B48F-1D18A9856A87
last_name: Roblek
orcid: 0000-0001-9588-1389
- first_name: Aparna
full_name: Ratheesh, Aparna
id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
last_name: Ratheesh
orcid: 0000-0001-7190-0776
- first_name: Katarina
full_name: Valosková, Katarina
id: 46F146FC-F248-11E8-B48F-1D18A9856A87
last_name: Valosková
orcid: 0000-0002-7926-0221
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
- first_name: Yutaka
full_name: Matsubayashi, Yutaka
last_name: Matsubayashi
- first_name: Besaiz
full_name: Sanchez Sanchez, Besaiz
last_name: Sanchez Sanchez
- first_name: Brian
full_name: Stramer, Brian
last_name: Stramer
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: 'György A, Roblek M, Ratheesh A, et al. Tools allowing independent visualization
and genetic manipulation of Drosophila melanogaster macrophages and surrounding
tissues. G3: Genes, Genomes, Genetics. 2018;8(3):845-857. doi:10.1534/g3.117.300452'
apa: 'György, A., Roblek, M., Ratheesh, A., Valosková, K., Belyaeva, V., Wachner,
S., … Siekhaus, D. E. (2018). Tools allowing independent visualization and genetic
manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3:
Genes, Genomes, Genetics. Genetics Society of America. https://doi.org/10.1534/g3.117.300452'
chicago: 'György, Attila, Marko Roblek, Aparna Ratheesh, Katarina Valosková, Vera
Belyaeva, Stephanie Wachner, Yutaka Matsubayashi, Besaiz Sanchez Sanchez, Brian
Stramer, and Daria E Siekhaus. “Tools Allowing Independent Visualization and Genetic
Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.”
G3: Genes, Genomes, Genetics. Genetics Society of America, 2018. https://doi.org/10.1534/g3.117.300452.'
ieee: 'A. György et al., “Tools allowing independent visualization and genetic
manipulation of Drosophila melanogaster macrophages and surrounding tissues,”
G3: Genes, Genomes, Genetics, vol. 8, no. 3. Genetics Society of America,
pp. 845–857, 2018.'
ista: 'György A, Roblek M, Ratheesh A, Valosková K, Belyaeva V, Wachner S, Matsubayashi
Y, Sanchez Sanchez B, Stramer B, Siekhaus DE. 2018. Tools allowing independent
visualization and genetic manipulation of Drosophila melanogaster macrophages
and surrounding tissues. G3: Genes, Genomes, Genetics. 8(3), 845–857.'
mla: 'György, Attila, et al. “Tools Allowing Independent Visualization and Genetic
Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.”
G3: Genes, Genomes, Genetics, vol. 8, no. 3, Genetics Society of America,
2018, pp. 845–57, doi:10.1534/g3.117.300452.'
short: 'A. György, M. Roblek, A. Ratheesh, K. Valosková, V. Belyaeva, S. Wachner,
Y. Matsubayashi, B. Sanchez Sanchez, B. Stramer, D.E. Siekhaus, G3: Genes, Genomes,
Genetics 8 (2018) 845–857.'
corr_author: '1'
date_created: 2018-12-11T11:47:05Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2026-04-27T22:30:48Z
day: '01'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.1534/g3.117.300452
ec_funded: 1
external_id:
isi:
- '000426693300011'
file:
- access_level: open_access
checksum: 7d9d28b915159078a4ca7add568010e8
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:11:48Z
date_updated: 2020-07-14T12:46:56Z
file_id: '4905'
file_name: IST-2018-990-v1+1_2018_Gyoergy_Tools_allowing.pdf
file_size: 2251222
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has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 845 - 857
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2637E9C0-B435-11E9-9278-68D0E5697425
grant_number: LSC16-021
name: Investigating the role of the novel major superfamily facilitator transporter
family member MFSD1 in metastasis
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
publication: 'G3: Genes, Genomes, Genetics'
publication_status: published
publisher: Genetics Society of America
publist_id: '7271'
pubrep_id: '990'
quality_controlled: '1'
related_material:
record:
- id: '6530'
relation: research_paper
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relation: research_paper
- id: '11193'
relation: dissertation_contains
status: public
- id: '6546'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Tools allowing independent visualization and genetic manipulation of Drosophila
melanogaster macrophages and surrounding tissues
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: 8
year: '2018'
...
---
OA_place: publisher
_id: '6263'
abstract:
- lang: eng
text: 'Antibiotic resistance can emerge spontaneously through genomic mutation and render
treatment ineffective. To counteract this process, in addition to the discovery and
description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand
its determinantsis needed. To address this challenge, this thesisuncoversnew genetic
determinants of resistance evolvability using a customized robotic setup,
exploressystematic ways in which resistance evolution is perturbed due to
dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates
the evolutionary fate of one specific type of evolvability modifier -a stress-induced
mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order
to identify them, we first developedan automated high-throughput feedback-controlled
protocol whichkeeps the population size and selection pressure approximately constant
for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic
concentration. We implementedthis protocol on a customized liquid handling robot and
propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100
generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more
compared to less sensitive ones. Our data uncover that deletions of certain genes
which do not affect mutation rate,including efflux pump components, a chaperone and
severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution.
Sequencing analysis of evolved populations indicates that epistasis with resistance
mutations is the most likelyexplanation. This work could inspire treatment strategies in
which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to
slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model,
toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence
evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations.
We show that in silicothis also leads to slower resistance evolution. We
see and confirm with experiments that increased mutation rates, apart from speeding
up evolution, also leadto high reproducibility of phenotypic adaptation in a context
of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic
resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier
–a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under
periodic selectionakin to clinical treatment. We set up a deterministic
infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and
evaluate various treatment schemes in how well they maintain a stress-induced
mutator allele. In particular,a high diversity of stresses is crucial for the persistence
of the mutator allele. This leads to a general trade-off where exactly those
diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly
evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular
mechanisms involved in antibiotic resistance evolution and could inspire new strategies
for slowing down its rate. '
acknowledged_ssus:
- _id: M-Shop
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Marta
full_name: Lukacisinova, Marta
id: 4342E402-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisinova
orcid: 0000-0002-2519-8004
citation:
ama: Lukacisinova M. Genetic determinants of antibiotic resistance evolution. 2018.
doi:10.15479/AT:ISTA:th1072
apa: Lukacisinova, M. (2018). Genetic determinants of antibiotic resistance evolution.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1072
chicago: Lukacisinova, Marta. “Genetic Determinants of Antibiotic Resistance Evolution.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1072.
ieee: M. Lukacisinova, “Genetic determinants of antibiotic resistance evolution,”
Institute of Science and Technology Austria, 2018.
ista: Lukacisinova M. 2018. Genetic determinants of antibiotic resistance evolution.
Institute of Science and Technology Austria.
mla: Lukacisinova, Marta. Genetic Determinants of Antibiotic Resistance Evolution.
Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1072.
short: M. Lukacisinova, Genetic Determinants of Antibiotic Resistance Evolution,
Institute of Science and Technology Austria, 2018.
corr_author: '1'
date_created: 2019-04-09T13:57:15Z
date_published: 2018-12-28T00:00:00Z
date_updated: 2026-04-08T14:15:06Z
day: '28'
ddc:
- '570'
- '576'
- '579'
degree_awarded: PhD
department:
- _id: ToBo
doi: 10.15479/AT:ISTA:th1072
file:
- access_level: open_access
checksum: fc60585c9eaad868ac007004ef130908
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T13:49:24Z
date_updated: 2021-02-11T11:17:17Z
embargo: 2020-01-25
file_id: '6264'
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file_size: 5656866
relation: main_file
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checksum: 264057ec0a92ab348cc83b41f021ba92
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-09T13:49:23Z
date_updated: 2020-07-14T12:47:25Z
embargo_to: open_access
file_id: '6265'
file_name: 2018_Thesis_Lukacisinova_source.docx
file_size: 5168054
relation: source_file
file_date_updated: 2021-02-11T11:17:17Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '91'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1027'
relation: part_of_dissertation
status: public
- id: '696'
relation: part_of_dissertation
status: public
- id: '1619'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: Genetic determinants of antibiotic resistance evolution
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2018'
...
---
_id: '1271'
abstract:
- lang: eng
text: 'Background: High directional persistence is often assumed to enhance the
efficiency of chemotactic migration. Yet, cells in vivo usually display meandering
trajectories with relatively low directional persistence, and the control and
function of directional persistence during cell migration in three-dimensional
environments are poorly understood. Results: Here, we use mesendoderm progenitors
migrating during zebrafish gastrulation as a model system to investigate the control
of directional persistence during migration in vivo. We show that progenitor cells
alternate persistent run phases with tumble phases that result in cell reorientation.
Runs are characterized by the formation of directed actin-rich protrusions and
tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions
or blebs leads to longer or shorter run phases, respectively. Importantly, both
reducing and increasing run phases result in larger spatial dispersion of the
cells, indicative of reduced migration precision. A physical model quantitatively
recapitulating the migratory behavior of mesendoderm progenitors indicates that
the ratio of tumbling to run times, and thus the specific degree of directional
persistence of migration, are critical for optimizing migration precision. Conclusions:
Together, our experiments and model provide mechanistic insight into the control
of migration directionality for cells moving in three-dimensional environments
that combine different protrusion types, whereby the proportion of blebs to actin-rich
protrusions determines the directional persistence and precision of movement by
regulating the ratio of tumbling to run times.'
acknowledged_ssus:
- _id: LifeSc
acknowledgement: "We thank K. Lee, C. Norden, A. Webb, and the members of the Paluch
lab for\r\ncomments on the manuscript. We are grateful to P. Rørth and Peter Dieterich\r\nfor
discussions, S. Ares, Y. Arboleda-Estudillo and S. Schneider for technical help,\r\nM.
Biro for help with programming, and the BIOTEC/MPI-CBG and IST zebrafish\r\nand
imaging facilities for help and advice at various stages of this project. This work
was supported by the Max Planck Society, the Medical Research Council UK (core funding
to the MRC LMCB), and by grants from the Polish Ministry of Science and Higher Education
(454/N-MPG/2009/0) to EKP, the Deutsche Forschungsgemeinschaft (HE 3231/6-1 and
PA 1590/1-1) to CPH and EKP, a A*Star JCO career development award (12302FG010)
to WY and a Damon Runyon fellowship award to ADM (DRG 2157-12). This work was also
supported by the Francis Crick Institute which receives its core funding from Cancer
Research UK (FC001317), the UK Medical Research Council (FC001317), and the Wellcome
Trust (FC001317) to GS."
article_number: '74'
article_processing_charge: No
author:
- first_name: Alba
full_name: Diz Muñoz, Alba
last_name: Diz Muñoz
- first_name: Pawel
full_name: Romanczuk, Pawel
last_name: Romanczuk
- first_name: Weimiao
full_name: Yu, Weimiao
last_name: Yu
- first_name: Martin
full_name: Bergert, Martin
last_name: Bergert
- first_name: Kenzo
full_name: Ivanovitch, Kenzo
last_name: Ivanovitch
- first_name: Guillame
full_name: Salbreux, Guillame
last_name: Salbreux
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
- first_name: Ewa
full_name: Paluch, Ewa
last_name: Paluch
citation:
ama: Diz Muñoz A, Romanczuk P, Yu W, et al. Steering cell migration by alternating
blebs and actin-rich protrusions. BMC Biology. 2016;14(1). doi:10.1186/s12915-016-0294-x
apa: Diz Muñoz, A., Romanczuk, P., Yu, W., Bergert, M., Ivanovitch, K., Salbreux,
G., … Paluch, E. (2016). Steering cell migration by alternating blebs and actin-rich
protrusions. BMC Biology. BioMed Central. https://doi.org/10.1186/s12915-016-0294-x
chicago: Diz Muñoz, Alba, Pawel Romanczuk, Weimiao Yu, Martin Bergert, Kenzo Ivanovitch,
Guillame Salbreux, Carl-Philipp J Heisenberg, and Ewa Paluch. “Steering Cell Migration
by Alternating Blebs and Actin-Rich Protrusions.” BMC Biology. BioMed Central,
2016. https://doi.org/10.1186/s12915-016-0294-x.
ieee: A. Diz Muñoz et al., “Steering cell migration by alternating blebs
and actin-rich protrusions,” BMC Biology, vol. 14, no. 1. BioMed Central,
2016.
ista: Diz Muñoz A, Romanczuk P, Yu W, Bergert M, Ivanovitch K, Salbreux G, Heisenberg
C-PJ, Paluch E. 2016. Steering cell migration by alternating blebs and actin-rich
protrusions. BMC Biology. 14(1), 74.
mla: Diz Muñoz, Alba, et al. “Steering Cell Migration by Alternating Blebs and Actin-Rich
Protrusions.” BMC Biology, vol. 14, no. 1, 74, BioMed Central, 2016, doi:10.1186/s12915-016-0294-x.
short: A. Diz Muñoz, P. Romanczuk, W. Yu, M. Bergert, K. Ivanovitch, G. Salbreux,
C.-P.J. Heisenberg, E. Paluch, BMC Biology 14 (2016).
date_created: 2018-12-11T11:51:04Z
date_published: 2016-09-02T00:00:00Z
date_updated: 2025-09-22T08:45:31Z
day: '02'
ddc:
- '572'
- '576'
department:
- _id: CaHe
doi: 10.1186/s12915-016-0294-x
external_id:
isi:
- '000382458900001'
file:
- access_level: open_access
checksum: 0bfa484ac69a0a560fb9a4589aeda7f6
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date_created: 2018-12-12T10:13:20Z
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month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 252064B8-B435-11E9-9278-68D0E5697425
grant_number: HE_3231/6-1
name: Analysis of the Formation and Function of Different Cell Protusion Types During
Cell Migration in Vivo
publication: BMC Biology
publication_status: published
publisher: BioMed Central
publist_id: '6049'
pubrep_id: '695'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Steering cell migration by alternating blebs and actin-rich protrusions
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 14
year: '2016'
...
---
_id: '1492'
abstract:
- lang: eng
text: To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated
cells with a preserved prolif eration capacity. The root pericycle represents
a unique tissue with conditional meristematic activity, and its tight control
determines initiation of lateral organs. Here we show that the meristematic activity
of the pericycle is constrained by the interaction with the adjacent endodermis.
Release of these restraints by elimination of endo dermal cells by single-cell
ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis
removal substitutes for the phytohormone auxin-dependent initiation of the pericycle
meristematic activity. However, auxin is indispensable to steer the cell division
plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally
distinct role for auxin during lateral root initiation. In the endodermis, auxin
releases constraints arising from cell-to-cell interactions that compromise the
pericycle meristematic activity, whereas, in the pericycle, auxin defines the
orientation of the cell division plane to initiate lateral roots.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'This work was supported by a European Research Council Starting
Inde-pendent Research grant (ERC-2007-Stg-207362-HCPO to J.D.), Research Foundation-Flanders
(G033711N to A.A.), and the Austrian Science Fund (FWF01_I1774S to E.B.). P.M. is
indebted to the Federation of European Biochemical Sciences for a Long-Term Fellowship. '
article_processing_charge: No
author:
- first_name: Peter
full_name: Marhavy, Peter
id: 3F45B078-F248-11E8-B48F-1D18A9856A87
last_name: Marhavy
orcid: 0000-0001-5227-5741
- first_name: Juan C
full_name: Montesinos López, Juan C
id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
last_name: Montesinos López
orcid: 0000-0001-9179-6099
- first_name: Anas
full_name: Abuzeineh, Anas
last_name: Abuzeineh
- first_name: Daniël
full_name: Van Damme, Daniël
last_name: Van Damme
- first_name: Joop
full_name: Vermeer, Joop
last_name: Vermeer
- first_name: Jérôme
full_name: Duclercq, Jérôme
last_name: Duclercq
- first_name: Hana
full_name: Rakusova, Hana
last_name: Rakusova
- first_name: Petra
full_name: Marhavá, Petra
id: 44E59624-F248-11E8-B48F-1D18A9856A87
last_name: Marhavá
- first_name: Jirí
full_name: Friml, Jirí
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
- first_name: Niko
full_name: Geldner, Niko
last_name: Geldner
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Marhavý P, Montesinos López JC, Abuzeineh A, et al. Targeted cell elimination
reveals an auxin-guided biphasic mode of lateral root initiation. Genes and
Development. 2016;30(4):471-483. doi:10.1101/gad.276964.115
apa: Marhavý, P., Montesinos López, J. C., Abuzeineh, A., Van Damme, D., Vermeer,
J., Duclercq, J., … Benková, E. (2016). Targeted cell elimination reveals an auxin-guided
biphasic mode of lateral root initiation. Genes and Development. Cold Spring
Harbor Laboratory Press. https://doi.org/10.1101/gad.276964.115
chicago: Marhavý, Peter, Juan C Montesinos López, Anas Abuzeineh, Daniël Van Damme,
Joop Vermeer, Jérôme Duclercq, Hana Rakusova, et al. “Targeted Cell Elimination
Reveals an Auxin-Guided Biphasic Mode of Lateral Root Initiation.” Genes and
Development. Cold Spring Harbor Laboratory Press, 2016. https://doi.org/10.1101/gad.276964.115.
ieee: P. Marhavý et al., “Targeted cell elimination reveals an auxin-guided
biphasic mode of lateral root initiation,” Genes and Development, vol.
30, no. 4. Cold Spring Harbor Laboratory Press, pp. 471–483, 2016.
ista: Marhavý P, Montesinos López JC, Abuzeineh A, Van Damme D, Vermeer J, Duclercq
J, Rakusova H, Marhavá P, Friml J, Geldner N, Benková E. 2016. Targeted cell elimination
reveals an auxin-guided biphasic mode of lateral root initiation. Genes and Development.
30(4), 471–483.
mla: Marhavý, Peter, et al. “Targeted Cell Elimination Reveals an Auxin-Guided Biphasic
Mode of Lateral Root Initiation.” Genes and Development, vol. 30, no. 4,
Cold Spring Harbor Laboratory Press, 2016, pp. 471–83, doi:10.1101/gad.276964.115.
short: P. Marhavý, J.C. Montesinos López, A. Abuzeineh, D. Van Damme, J. Vermeer,
J. Duclercq, H. Rakusova, P. Marhavá, J. Friml, N. Geldner, E. Benková, Genes
and Development 30 (2016) 471–483.
corr_author: '1'
date_created: 2018-12-11T11:52:20Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2025-09-18T11:14:08Z
day: '01'
ddc:
- '570'
department:
- _id: EvBe
doi: 10.1101/gad.276964.115
external_id:
isi:
- '000370131500009'
pmid:
- ' 26883363'
file:
- access_level: open_access
checksum: ea394498ee56270e021d1028a29358a0
content_type: application/pdf
creator: kschuh
date_created: 2019-01-25T09:56:11Z
date_updated: 2020-07-14T12:44:58Z
file_id: '5883'
file_name: 2016_GeneDev_Marhavy.pdf
file_size: 2757636
relation: main_file
file_date_updated: 2020-07-14T12:44:58Z
has_accepted_license: '1'
intvolume: ' 30'
isi: 1
issue: '4'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '03'
oa: 1
oa_version: Published Version
page: 471 - 483
pmid: 1
publication: Genes and Development
publication_status: published
publisher: Cold Spring Harbor Laboratory Press
publist_id: '5691'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Targeted cell elimination reveals an auxin-guided biphasic mode of lateral
root initiation
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 30
year: '2016'
...
---
OA_place: publisher
_id: '1129'
abstract:
- lang: eng
text: "Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms.
Despite its importance, basic questions regarding force transduction\r\nor directional
sensing are still heavily investigated. Directed migration of cells\r\nguided
by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as
embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al.,
2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise
adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009),
or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton
et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment
sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic
migration by inducing adhesion to adhesive ligands and directional\r\nguidance
(Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the
cellular response to immobilized guidance cues requires in vitro assays\r\nthat
foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular
scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration
of haptotactic cell migration through design and employment of such\r\nassays
represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes,
which after encountering danger\r\nsignals such as pathogens in peripheral organs
instruct naïve T-cells and\r\nconsequently the adaptive immune response in the
lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery,
DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber
et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients
have not yet been addressed. The main reason for this is the lack of\r\nan assay
that offers diverse haptotactic environments, hence allowing the study\r\nof DC
migration as a response to different signals of immobilized guidance cue.\r\nIn
this work, we developed an in vitro assay that enables us to\r\nquantitatively
assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning
with physically confining migration conditions. With this tool at hand, we studied
the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis.
We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration
in combination with the local\r\nsteepness of the gradient. Our analysis suggests
that the directionality of\r\nmigrating DCs is governed by the signal-to-noise
ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21
gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic
guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also
able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To
this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which
is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization
(Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial
for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm
those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic
guidance cues\r\noften coincide and compete with soluble chemotactic guidance
cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive
cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating
DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing
chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess
these complex coinciding immobilized and soluble\r\nguidance cues, we implemented
our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing
for chemotactic gradient generation. To validate\r\nthe assay, we observed DC
migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis
has been studied intensively over the\r\nlast century. However, quantitative studies
leading to conceptual models are\r\nlargely missing, again due to the lack of
a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro
assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished
by stable passivation of the surface. In\r\naddition, controlled adhesion must
be sustainable, quantifiable and dose\r\ndependent in order to create homogenous
gradients. Therefore, we developed a novel covalent photo-patterning technique
satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol
(PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to
direct cell migration. This\r\napproach allowed us to characterize the haptotactic
migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined
patterns of adhesive cue\r\nallowed us to control for cell shape and growth on
a subcellular scale."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
acknowledgement: "First, I would like to thank Michael Sixt for being a great supervisor,
mentor and\r\nscientist. I highly appreciate his guidance and continued support.
Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to
pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe
sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel
Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice
and encouragement during our regular progress meetings.\r\nI also want to thank
the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for
amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant
factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere
as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank
my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries,
Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf,
Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz,
Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing
time with many\r\nlegendary evenings and events. Along these lines I want to thank
the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions.
I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank
the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches.
In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens,
Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny,
Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful
after-lunch matches.\r\nI would not have been able to analyze the thousands of cell
trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration
with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings,
discussions and graphs and of course for proofreading and\r\nadvice for this thesis.
For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like
to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing
me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS
coated coverslips and help with anything\r\nmicro-fabrication related. And Maria
Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her
it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva,
Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility
as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for
excellent technical support. At this\r\npoint I especially want to thank Robert
for countless image analyses and\r\ntechnical ideas. Always interested and creative
he played an essential role in all\r\nof my projects.\r\nAdditionally I want to
thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for
scientific and especially mental support in all\r\nthose years, countless coffee
sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
citation:
ama: Schwarz J. Quantitative analysis of haptotactic cell migration. 2016.
apa: Schwarz, J. (2016). Quantitative analysis of haptotactic cell migration.
Institute of Science and Technology Austria.
chicago: Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute
of Science and Technology Austria, 2016.
ieee: J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute
of Science and Technology Austria, 2016.
ista: Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute
of Science and Technology Austria.
mla: Schwarz, Jan. Quantitative Analysis of Haptotactic Cell Migration. Institute
of Science and Technology Austria, 2016.
short: J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute
of Science and Technology Austria, 2016.
corr_author: '1'
date_created: 2018-12-11T11:50:18Z
date_published: 2016-07-01T00:00:00Z
date_updated: 2026-04-08T14:28:53Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
file:
- access_level: closed
checksum: e3cd6b28f9c5cccb8891855565a2dade
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creator: dernst
date_created: 2019-08-13T10:55:35Z
date_updated: 2019-08-13T10:55:35Z
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checksum: c3dbe219acf87eed2f46d21d5cca00de
content_type: application/pdf
creator: dernst
date_created: 2021-02-22T11:43:14Z
date_updated: 2021-02-22T11:43:14Z
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file_size: 8396717
relation: main_file
success: 1
file_date_updated: 2021-02-22T11:43:14Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '178'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6231'
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: Quantitative analysis of haptotactic cell migration
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2016'
...
---
_id: '1640'
abstract:
- lang: eng
text: Auxin and cytokinin are key endogenous regulators of plant development. Although
cytokinin-mediated modulation of auxin distribution is a developmentally crucial
hormonal interaction, its molecular basis is largely unknown. Here we show a direct
regulatory link between cytokinin signalling and the auxin transport machinery
uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that
the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin
perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters
at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory
element effectively uncouples PIN transcription from the CRF-mediated cytokinin
regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent
a missing cross-talk component that fine-tunes auxin transport capacity downstream
of cytokinin signalling to control plant development.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: This work was supported by the European Research Council Starting
Independent Research grant (ERC-2007-Stg-207362-HCPO to E.B., M.S., C.C.), by the
Ghent University Multidisciplinary Research Partnership ‘Biotechnology for a Sustainable
Economy’ no.01MRB510W, by the Research Foundation—Flanders (grant 3G033711 to J.-A.O.),
by the Austrian Science Fund (FWF01_I1774S) to K.Ö.,E.B., and by the Interuniversity
Attraction Poles Programme (IUAP P7/29 ‘MARS’) initiated by the Belgian Science
Policy Office. I.D.C. and S.V. are post-doctoral fellows of the Research Foundation—Flanders
(FWO). This research was supported by the Scientific Service Units (SSU) of IST-Austria
through resources provided by the Bioimaging Facility (BIF), the Life Science Facility
(LSF).
article_number: '8717'
article_processing_charge: No
author:
- first_name: Mária
full_name: Šimášková, Mária
last_name: Šimášková
- first_name: José
full_name: O'Brien, José
last_name: O'Brien
- first_name: Mamoona
full_name: Khan-Djamei, Mamoona
id: 391B5BBC-F248-11E8-B48F-1D18A9856A87
last_name: Khan-Djamei
- first_name: Giel
full_name: Van Noorden, Giel
last_name: Van Noorden
- first_name: Krisztina
full_name: Ötvös, Krisztina
id: 29B901B0-F248-11E8-B48F-1D18A9856A87
last_name: Ötvös
orcid: 0000-0002-5503-4983
- first_name: Anne
full_name: Vieten, Anne
last_name: Vieten
- first_name: Inge
full_name: De Clercq, Inge
last_name: De Clercq
- first_name: Johanna
full_name: Van Haperen, Johanna
last_name: Van Haperen
- first_name: Candela
full_name: Cuesta, Candela
id: 33A3C818-F248-11E8-B48F-1D18A9856A87
last_name: Cuesta
orcid: 0000-0003-1923-2410
- first_name: Klára
full_name: Hoyerová, Klára
last_name: Hoyerová
- first_name: Steffen
full_name: Vanneste, Steffen
last_name: Vanneste
- first_name: Peter
full_name: Marhavy, Peter
id: 3F45B078-F248-11E8-B48F-1D18A9856A87
last_name: Marhavy
orcid: 0000-0001-5227-5741
- first_name: Krzysztof T
full_name: Wabnik, Krzysztof T
id: 4DE369A4-F248-11E8-B48F-1D18A9856A87
last_name: Wabnik
orcid: 0000-0001-7263-0560
- first_name: Frank
full_name: Van Breusegem, Frank
last_name: Van Breusegem
- first_name: Moritz
full_name: Nowack, Moritz
last_name: Nowack
- first_name: Angus
full_name: Murphy, Angus
last_name: Murphy
- first_name: Jiřĺ
full_name: Friml, Jiřĺ
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
- first_name: Dolf
full_name: Weijers, Dolf
last_name: Weijers
- first_name: Tom
full_name: Beeckman, Tom
last_name: Beeckman
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Šimášková M, O’Brien J, Khan-Djamei M, et al. Cytokinin response factors regulate
PIN-FORMED auxin transporters. Nature Communications. 2015;6. doi:10.1038/ncomms9717
apa: Šimášková, M., O’Brien, J., Khan-Djamei, M., Van Noorden, G., Ötvös, K., Vieten,
A., … Benková, E. (2015). Cytokinin response factors regulate PIN-FORMED auxin
transporters. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms9717
chicago: Šimášková, Mária, José O’Brien, Mamoona Khan-Djamei, Giel Van Noorden,
Krisztina Ötvös, Anne Vieten, Inge De Clercq, et al. “Cytokinin Response Factors
Regulate PIN-FORMED Auxin Transporters.” Nature Communications. Nature
Publishing Group, 2015. https://doi.org/10.1038/ncomms9717.
ieee: M. Šimášková et al., “Cytokinin response factors regulate PIN-FORMED
auxin transporters,” Nature Communications, vol. 6. Nature Publishing Group,
2015.
ista: Šimášková M, O’Brien J, Khan-Djamei M, Van Noorden G, Ötvös K, Vieten A, De
Clercq I, Van Haperen J, Cuesta C, Hoyerová K, Vanneste S, Marhavý P, Wabnik KT,
Van Breusegem F, Nowack M, Murphy A, Friml J, Weijers D, Beeckman T, Benková E.
2015. Cytokinin response factors regulate PIN-FORMED auxin transporters. Nature
Communications. 6, 8717.
mla: Šimášková, Mária, et al. “Cytokinin Response Factors Regulate PIN-FORMED Auxin
Transporters.” Nature Communications, vol. 6, 8717, Nature Publishing Group,
2015, doi:10.1038/ncomms9717.
short: M. Šimášková, J. O’Brien, M. Khan-Djamei, G. Van Noorden, K. Ötvös, A. Vieten,
I. De Clercq, J. Van Haperen, C. Cuesta, K. Hoyerová, S. Vanneste, P. Marhavý,
K.T. Wabnik, F. Van Breusegem, M. Nowack, A. Murphy, J. Friml, D. Weijers, T.
Beeckman, E. Benková, Nature Communications 6 (2015).
corr_author: '1'
date_created: 2018-12-11T11:53:12Z
date_published: 2015-01-01T00:00:00Z
date_updated: 2025-09-23T08:24:11Z
day: '01'
ddc:
- '580'
department:
- _id: EvBe
- _id: JiFr
doi: 10.1038/ncomms9717
ec_funded: 1
external_id:
isi:
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project:
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call_identifier: FP7
grant_number: '207362'
name: Hormonal cross-talk in plant organogenesis
- _id: 2542D156-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I 1774-B16
name: Hormone cross-talk drives nutrient dependent plant development
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
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title: Cytokinin response factors regulate PIN-FORMED auxin transporters
type: journal_article
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...