---
OA_place: publisher
_id: '20357'
acknowledged_ssus:
- _id: ScienComp
- _id: E-Lib
acknowledgement: "I would also like to acknowledge the Austrian Academy of Sciences
  for funding through the\r\nDOC Fellowship program (fellowship number 26917), the
  Grants Office at ISTA for their\r\nassistance with the application, and the Scientific
  Computing Unit for their support regarding\r\nhigh-performance computation.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Natalia
  full_name: Ruzickova, Natalia
  id: D2761128-D73D-11E9-A1BF-BA0DE6697425
  last_name: Ruzickova
citation:
  ama: Ruzickova N. Effect propagation in biological networks. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20357">10.15479/AT-ISTA-20357</a>
  apa: Ruzickova, N. (2025). <i>Effect propagation in biological networks</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20357">https://doi.org/10.15479/AT-ISTA-20357</a>
  chicago: Ruzickova, Natalia. “Effect Propagation in Biological Networks.” Institute
    of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20357">https://doi.org/10.15479/AT-ISTA-20357</a>.
  ieee: N. Ruzickova, “Effect propagation in biological networks,” Institute of Science
    and Technology Austria, 2025.
  ista: Ruzickova N. 2025. Effect propagation in biological networks. Institute of
    Science and Technology Austria.
  mla: Ruzickova, Natalia. <i>Effect Propagation in Biological Networks</i>. Institute
    of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20357">10.15479/AT-ISTA-20357</a>.
  short: N. Ruzickova, Effect Propagation in Biological Networks, Institute of Science
    and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-09-15T17:04:48Z
date_published: 2025-09-15T00:00:00Z
date_updated: 2026-10-02T10:15:31Z
day: '15'
ddc:
- '570'
- '530'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaTk
doi: 10.15479/AT-ISTA-20357
doi_confirm: '1'
file:
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  checksum: 0582508d439b233497384f83a8307398
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  date_created: 2026-08-07T10:57:05Z
  date_updated: 2026-09-15T22:30:02Z
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file_date_updated: 2026-09-15T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20357
has_accepted_license: '1'
keyword:
- gene regulation
- networks
- omnigenic model
- pancreas
- collective behaviour
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '156'
project:
- _id: 7bec9174-9f16-11ee-852c-ded9fe5f810e
  name: Collective behaviour of cells in pancreatic Islets of Langerhans
publication_identifier:
  isbn:
  - 978-3-99078-066-4
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '18525'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
title: Effect propagation in biological networks
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: publisher
_id: '20563'
abstract:
- lang: eng
  text: "The theory of optimal transport provides an elegant and powerful description
    of many evolution\r\nequations as gradient flows. The primary objective of this
    thesis is to adapt and extend the\r\ntheory to deal with important equations that
    are not covered by the classical framework,\r\nspecifically boundary value problems
    and kinetic equations. Additionally, we establish new\r\nresults in periodic homogenization
    for discrete dynamical optimal transport and in quantization\r\nof measures.\r\nSection
    1.1 serves as an invitation to the classical theory of optimal transport, including
    the\r\nmain definitions and a selection of well-established theorems. Sections
    1.2-1.5 introduce the\r\nmain results of this thesis, outline the motivations,
    and review the current state of the art.\r\nIn Chapter 2, we consider the Fokker–Planck
    equation on a bounded set with positive Dirichlet\r\nboundary conditions. We construct
    a time-discrete scheme involving a modification of the\r\nWasserstein distance
    and, under weak assumptions, prove its convergence to a solution of this\r\nboundary
    value problem. In dimension 1, we show that this solution is a gradient flow in
    a\r\nsuitable space of measures.\r\nChapter 3 presents joint work with Giovanni
    Brigati and Jan Maas. We introduce a new theory\r\nof optimal transport to describe
    and study particle systems at the mesoscopic scale. We prove\r\nadapted versions
    of some fundamental theorems, including the Benamou–Brenier formula and\r\nthe
    identification of absolutely continuous curves of measures.\r\nChapter 4 presents
    joint work with Lorenzo Portinale. We prove convergence of dynamical\r\ntransportation
    functionals on periodic graphs in the large-scale limit when the cost functional\r\nis
    asymptotically linear. Additionally, we show that discrete 1-Wasserstein distances
    converge\r\nto 1-Wasserstein distances constructed from crystalline norms on R\r\nd\r\n.\r\nChapter
    5 concerns optimal empirical quantization: the problem of approximating a measure\r\nby
    the sum of n equally weighted Dirac deltas, so as to minimize the error in the
    p-Wasserstein\r\ndistance. Our main result is an analog of Zador’s theorem, providing
    asymptotic bounds for\r\nthe minimal error as n tends to infinity.\r\n"
acknowledgement: "The research contained in this thesis has received funding from
  the Austrian Science\r\nFund (FWF) project 10.55776/F65."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Filippo
  full_name: Quattrocchi, Filippo
  id: 3ebd6ba8-edfb-11eb-afb5-91a9745ba308
  last_name: Quattrocchi
  orcid: 0009-0000-9773-1931
citation:
  ama: Quattrocchi F. Optimal transport methods for kinetic equations, boundary value
    problems, and discretization of measures. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20563">10.15479/AT-ISTA-20563</a>
  apa: Quattrocchi, F. (2025). <i>Optimal transport methods for kinetic equations,
    boundary value problems, and discretization of measures</i>. Institute of Science
    and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20563">https://doi.org/10.15479/AT-ISTA-20563</a>
  chicago: Quattrocchi, Filippo. “Optimal Transport Methods for Kinetic Equations,
    Boundary Value Problems, and Discretization of Measures.” Institute of Science
    and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20563">https://doi.org/10.15479/AT-ISTA-20563</a>.
  ieee: F. Quattrocchi, “Optimal transport methods for kinetic equations, boundary
    value problems, and discretization of measures,” Institute of Science and Technology
    Austria, 2025.
  ista: Quattrocchi F. 2025. Optimal transport methods for kinetic equations, boundary
    value problems, and discretization of measures. Institute of Science and Technology
    Austria.
  mla: Quattrocchi, Filippo. <i>Optimal Transport Methods for Kinetic Equations, Boundary
    Value Problems, and Discretization of Measures</i>. Institute of Science and Technology
    Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20563">10.15479/AT-ISTA-20563</a>.
  short: F. Quattrocchi, Optimal Transport Methods for Kinetic Equations, Boundary
    Value Problems, and Discretization of Measures, Institute of Science and Technology
    Austria, 2025.
corr_author: '1'
date_created: 2025-10-28T13:10:49Z
date_published: 2025-11-03T00:00:00Z
date_updated: 2026-10-02T11:24:55Z
day: '03'
ddc:
- '515'
- '519'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JaMa
doi: 10.15479/AT-ISTA-20563
file:
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  creator: fquattro
  date_created: 2025-11-17T21:04:15Z
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file_date_updated: 2026-01-01T23:30:03Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20563
has_accepted_license: '1'
keyword:
- optimal transport
- kinetic equations
- boundary value problems
- quantization
- gradient flows
- homogenization
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '240'
project:
- _id: 260482E2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: F06504
  name: Taming Complexity in Partial Differential Systems
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '20569'
    relation: part_of_dissertation
    status: public
  - id: '20571'
    relation: part_of_dissertation
    status: public
  - id: '20570'
    relation: part_of_dissertation
    status: public
  - id: '18706'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Jan
  full_name: Maas, Jan
  id: 4C5696CE-F248-11E8-B48F-1D18A9856A87
  last_name: Maas
  orcid: 0000-0002-0845-1338
title: Optimal transport methods for kinetic equations, boundary value problems, and
  discretization of measures
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: repository
OA_type: green
_id: '20569'
abstract:
- lang: eng
  text: 'This is the first part of a general description in terms of mass transport
    for time-evolving interacting particles systems, at a mesoscopic level. Beyond
    kinetic theory, our framework naturally applies in biology, computer vision, and
    engineering. The central object of our study is a new discrepancy d between two
    probability distributions in position and velocity states, which is reminiscent
    of the 2-Wasserstein distance, but of second-order nature. We construct d in two
    steps. First, we optimise over transport plans. The cost function is given by
    the minimal acceleration between two coupled states on a fixed time horizon T.
    Second, we further optimise over the time horizon T > 0. We prove the existence
    of optimal transport plans and maps, and study two time-continuous characterisations
    of d. One is given in terms of dynamical transport plans. The other one -- in
    the spirit of the Benamou--Brenier formula -- is formulated as the minimisation
    of an action of the acceleration field, constrained by Vlasov''s equations. Equivalence
    of static and dynamical formulations of d holds true. While part of this result
    can be derived from recent, parallel developments in optimal control between measures,
    we give an original proof relying on two new ingredients: Galilean regularisation
    of Vlasov''s equations and a kinetic Monge--Mather shortening principle. Finally,
    we establish a first-order differential calculus in the geometry induced by d,
    and identify solutions to Vlasov''s equations with curves of measures satisfying
    a certain d-absolute continuity condition. One consequence is an explicit formula
    for the d-derivative of such curves.'
acknowledgement: "This work was partially inspired by an unpublished note from 2014
  by Guillaume Carlier,\r\nJean Dolbeault, and Bruno Nazaret. GB deeply thanks Jean
  Dolbeault for proposing\r\nthis problem to him, guiding him into the subject, and
  sharing the aforementioned note.\r\nWe are grateful to Karthik Elamvazhuthi for
  making us aware of the work [20].\r\nThe work of GB has received funding from the
  European Union’s Horizon 2020 research and innovation programme under the Marie
  Sklodowska-Curie grant agreement\r\nNo 101034413.\r\nJM and FQ gratefully acknowledge
  support from the Austrian Science Fund (FWF)\r\nproject 10.55776/F65."
article_number: '2502.15665'
article_processing_charge: No
arxiv: 1
author:
- first_name: Giovanni
  full_name: Brigati, Giovanni
  id: 63ff57e8-1fbb-11ee-88f2-f558ffc59cf1
  last_name: Brigati
- first_name: Jan
  full_name: Maas, Jan
  id: 4C5696CE-F248-11E8-B48F-1D18A9856A87
  last_name: Maas
  orcid: 0000-0002-0845-1338
- first_name: Filippo
  full_name: Quattrocchi, Filippo
  id: 3ebd6ba8-edfb-11eb-afb5-91a9745ba308
  last_name: Quattrocchi
  orcid: 0009-0000-9773-1931
citation:
  ama: 'Brigati G, Maas J, Quattrocchi F. Kinetic Optimal Transport (OTIKIN) -- Part
    1: Second-order discrepancies between probability measures. <i>arXiv</i>. doi:<a
    href="https://doi.org/10.48550/arXiv.2502.15665">10.48550/arXiv.2502.15665</a>'
  apa: 'Brigati, G., Maas, J., &#38; Quattrocchi, F. (n.d.). Kinetic Optimal Transport
    (OTIKIN) -- Part 1: Second-order discrepancies between probability measures. <i>arXiv</i>.
    <a href="https://doi.org/10.48550/arXiv.2502.15665">https://doi.org/10.48550/arXiv.2502.15665</a>'
  chicago: 'Brigati, Giovanni, Jan Maas, and Filippo Quattrocchi. “Kinetic Optimal
    Transport (OTIKIN) -- Part 1: Second-Order Discrepancies between Probability Measures.”
    <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2502.15665">https://doi.org/10.48550/arXiv.2502.15665</a>.'
  ieee: 'G. Brigati, J. Maas, and F. Quattrocchi, “Kinetic Optimal Transport (OTIKIN)
    -- Part 1: Second-order discrepancies between probability measures,” <i>arXiv</i>.
    .'
  ista: 'Brigati G, Maas J, Quattrocchi F. Kinetic Optimal Transport (OTIKIN) -- Part
    1: Second-order discrepancies between probability measures. arXiv, 2502.15665.'
  mla: 'Brigati, Giovanni, et al. “Kinetic Optimal Transport (OTIKIN) -- Part 1: Second-Order
    Discrepancies between Probability Measures.” <i>ArXiv</i>, 2502.15665, doi:<a
    href="https://doi.org/10.48550/arXiv.2502.15665">10.48550/arXiv.2502.15665</a>.'
  short: G. Brigati, J. Maas, F. Quattrocchi, ArXiv (n.d.).
corr_author: '1'
date_created: 2025-10-28T13:12:08Z
date_published: 2025-08-10T00:00:00Z
date_updated: 2026-11-04T23:31:11Z
day: '10'
department:
- _id: GradSch
- _id: JaMa
doi: 10.48550/arXiv.2502.15665
ec_funded: 1
external_id:
  arxiv:
  - '2502.15665'
fulldoi: https://doi.org/10.48550/arXiv.2502.15665
keyword:
- optimal transport
- kinetic theory
- second-order discrepancy
- Vlasov equation
- Wasserstein splines.
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2502.15665
month: '08'
oa: 1
oa_version: Preprint
project:
- _id: fc31cba2-9c52-11eb-aca3-ff467d239cd2
  grant_number: F6504
  name: Taming Complexity in Partial Differential Systems
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
  call_identifier: H2020
  grant_number: '101034413'
  name: 'IST-BRIDGE: International postdoctoral program'
publication: arXiv
publication_status: draft
related_material:
  record:
  - id: '20563'
    relation: dissertation_contains
    status: public
status: public
title: 'Kinetic Optimal Transport (OTIKIN) -- Part 1: Second-order discrepancies between
  probability measures'
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '19533'
abstract:
- lang: eng
  text: "This thesis explores advancements in quantum remote sensing and non-equilibrium
    phase\r\ntransitions in the microwave regime, with a focus on dissipative phase
    transitions and quantumenhanced sensing.\r\nIn the first project, I experimentally
    studied photon blockade breakdown as a dissipative phase\r\ntransition in a zero-dimensional
    cavity-qubit system. By defining an appropriate thermodynamic\r\nlimit, we demonstrated
    that the observed bistability is a genuine signature of a first-order\r\nphase
    transition in this system. This work provides insight into non-equilibrium quantum\r\ndynamics
    and phase transitions in driven-dissipative open quantum systems.\r\nThe second
    project focuses on the experimental realization of a phase-conjugate receiver
    for\r\nquantum illumination (QI), a quantum sensing protocol that enhances target
    detection in noisy\r\nenvironments using entangled light. While an ideal spontaneous
    parametric down-conversion\r\n(SPDC) source and receiver could, in theory, provide
    up to a 6 dB advantage over classical\r\nillumination, no such ideal receiver
    exists. Instead, we explore an experimental realization of a\r\nphase-conjugate
    receiver for QI in the microwave regime at millikelvin temperatures using a\r\nJosephson
    parametric converter (JPC) as a source of continuous-variable Gaussian entangled\r\nsignal-idler
    pairs, where a maximum 3 dB advantage is theoretically achievable. We investigate\r\nkey
    experimental limitations that constrain practical QI performance, contributing
    to the\r\ndevelopment of quantum-enhanced sensing.\r\nAdditionally, this thesis
    presents efficient digital signal processing (DSP) techniques implemented in C++
    and Python in collaboration with Przemysław Zieliński and Luka Drmić. These\r\nmethods,
    optimized using the Intel Integrated Performance Primitives (IPP) library, have
    been\r\nessential in data acquisition, noise filtering, and correlation analysis
    across multiple research\r\nprojects. Although not real-time, these DSP techniques
    significantly enhance the accuracy of\r\nquantum measurements.\r\nOverall, this
    thesis advances quantum-enhanced sensing by establishing the thermodynamic\r\nlimit
    in a single transmon-cavity system and experimentally exploring a phase-conjugate
    receiver\r\nfor QI. These findings contribute to quantum metrology, particularly
    for weak signal detection\r\nand remote sensing in noisy environments.\r\n"
acknowledged_ssus:
- _id: ScienComp
- _id: M-Shop
- _id: NanoFab
- _id: LifeSc
- _id: SSU
acknowledgement: "I acknowledge the generous financial support of the Austrian Science
  Fund (FWF) via BeyondC\r\n(F7105) and the European Union’s Horizon 2020 research
  and innovation program (FETopen\r\nQUARTET, Grant Agreement No. 862644), which made
  this research possible. I also extend\r\nmy sincere appreciation to the MIBA workshop
  and the Institute of Science and Technology\r\nAustria nanofabrication facility
  for their technical assistance, which was instrumental in realizing\r\nthis work."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Riya
  full_name: Sett, Riya
  id: 2E6D040E-F248-11E8-B48F-1D18A9856A87
  last_name: Sett
  orcid: 0000-0001-7641-8348
citation:
  ama: Sett R. Quantum remote sensing and non-equilibrium phase transitions in the
    microwave regime. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19533">10.15479/AT-ISTA-19533</a>
  apa: Sett, R. (2025). <i>Quantum remote sensing and non-equilibrium phase transitions
    in the microwave regime</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-19533">https://doi.org/10.15479/AT-ISTA-19533</a>
  chicago: Sett, Riya. “Quantum Remote Sensing and Non-Equilibrium Phase Transitions
    in the Microwave Regime.” Institute of Science and Technology Austria, 2025. <a
    href="https://doi.org/10.15479/AT-ISTA-19533">https://doi.org/10.15479/AT-ISTA-19533</a>.
  ieee: R. Sett, “Quantum remote sensing and non-equilibrium phase transitions in
    the microwave regime,” Institute of Science and Technology Austria, 2025.
  ista: Sett R. 2025. Quantum remote sensing and non-equilibrium phase transitions
    in the microwave regime. Institute of Science and Technology Austria.
  mla: Sett, Riya. <i>Quantum Remote Sensing and Non-Equilibrium Phase Transitions
    in the Microwave Regime</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-19533">10.15479/AT-ISTA-19533</a>.
  short: R. Sett, Quantum Remote Sensing and Non-Equilibrium Phase Transitions in
    the Microwave Regime, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-04-09T16:44:26Z
date_published: 2025-04-01T00:00:00Z
date_updated: 2026-10-15T09:08:00Z
day: '1'
ddc:
- '530'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoFi
doi: 10.15479/AT-ISTA-19533
doi_confirm: '1'
ec_funded: 1
file:
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  checksum: ba6cd2289d0141a160a14fc97df1632f
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  date_updated: 2025-10-11T22:30:02Z
  embargo: 2025-10-11
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file_date_updated: 2025-10-11T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-19533
has_accepted_license: '1'
keyword:
- phase transition
- open quantum system
- phase diagram
- cavity quantum electrodynamics
- superconducting qubits
- semiclassical physics
- quantum optics
- josephson junction
- parametric converter
- phase conjugation
- quantum radar
- quantum entanglement
- correlation
- quantum sensing
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '109'
project:
- _id: 237CBA6C-32DE-11EA-91FC-C7463DDC885E
  call_identifier: H2020
  grant_number: '862644'
  name: Quantum readout techniques and technologies
- _id: bdb108fd-d553-11ed-ba76-83dc74a9864f
  grant_number: F07105
  name: QUANTUM INFORMATION SYSTEMS BEYOND CLASSICAL CAPABILITIES / P5- Integration
    of Superconducting Quantum Circuits
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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    relation: research_data
    status: public
  - id: '19280'
    relation: part_of_dissertation
    status: public
  - id: '13117'
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    status: public
  - id: '17183'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Johannes M
  full_name: Fink, Johannes M
  id: 4B591CBA-F248-11E8-B48F-1D18A9856A87
  last_name: Fink
  orcid: 0000-0001-8112-028X
title: Quantum remote sensing and non-equilibrium phase transitions in the microwave
  regime
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '19280'
abstract:
- lang: eng
  text: Recent advancements in superconducting circuits have enabled the experimental
    study of collective behavior of precisely controlled intermediate-scale ensembles
    of qubits. In this work, we demonstrate an atomic frequency comb formed by individual
    artificial atoms strongly coupled to a single resonator mode. We observe periodic
    microwave pulses that originate from a single coherent excitation dynamically
    interacting with the multiqubit ensemble. We show that this revival dynamics emerges
    as a consequence of the constructive and periodic rephasing of the five superconducting
    qubits forming the vacuum Rabi split comb. In the future, similar devices could
    be used as a memory with in situ tunable storage time or as an on-chip periodic
    pulse generator with nonclassical photon statistics.
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
acknowledgement: 'The authors thank G. Arnold and R. Sahu for the discussions, L.
  Drmic for software development, the MIBA workshop and the ISTA nanofabrication facility
  for technical support, and VTT Technical Research Centre of Finland for providing
  us TWPAs for follow-up measurements. This work was supported by the Austrian Science
  Fund (FWF) [Grant DOI: 10.55776/F71] through BeyondC (F7105) and IST Austria. E. S. R.
  is the recipient of a DOC fellowship of the Austrian Academy of Sciences at IST
  Austria. J. M. F. and M. Ž. acknowledge support from the European Research Council
  under Grant Agreement No. 758053 (ERC StG QUNNECT) and a NOMIS foundation research
  grant.'
article_number: '063601'
article_processing_charge: Yes (via OA deal)
article_type: original
arxiv: 1
author:
- first_name: Elena
  full_name: Redchenko, Elena
  id: 2C21D6E8-F248-11E8-B48F-1D18A9856A87
  last_name: Redchenko
- first_name: M.
  full_name: Zens, M.
  last_name: Zens
- first_name: Martin
  full_name: Zemlicka, Martin
  id: 2DCF8DE6-F248-11E8-B48F-1D18A9856A87
  last_name: Zemlicka
  orcid: 0009-0005-0878-3032
- first_name: Matilda
  full_name: Peruzzo, Matilda
  id: 3F920B30-F248-11E8-B48F-1D18A9856A87
  last_name: Peruzzo
  orcid: 0000-0002-3415-4628
- first_name: Farid
  full_name: Hassani, Farid
  id: 2AED110C-F248-11E8-B48F-1D18A9856A87
  last_name: Hassani
  orcid: 0000-0001-6937-5773
- first_name: Riya
  full_name: Sett, Riya
  id: 2E6D040E-F248-11E8-B48F-1D18A9856A87
  last_name: Sett
  orcid: 0000-0001-7641-8348
- first_name: Przemyslaw D
  full_name: Zielinski, Przemyslaw D
  id: e198fcc4-f6e0-11ea-865d-b6a256760ee8
  last_name: Zielinski
- first_name: H. S.
  full_name: Dhar, H. S.
  last_name: Dhar
- first_name: D. O.
  full_name: Krimer, D. O.
  last_name: Krimer
- first_name: S.
  full_name: Rotter, S.
  last_name: Rotter
- first_name: Johannes M
  full_name: Fink, Johannes M
  id: 4B591CBA-F248-11E8-B48F-1D18A9856A87
  last_name: Fink
  orcid: 0000-0001-8112-028X
citation:
  ama: Redchenko E, Zens M, Zemlicka M, et al. Observation of collapse and revival
    in a superconducting atomic frequency comb. <i>Physical Review Letters</i>. 2025;134(6).
    doi:<a href="https://doi.org/10.1103/PhysRevLett.134.063601">10.1103/PhysRevLett.134.063601</a>
  apa: Redchenko, E., Zens, M., Zemlicka, M., Peruzzo, M., Hassani, F., Sett, R.,
    … Fink, J. M. (2025). Observation of collapse and revival in a superconducting
    atomic frequency comb. <i>Physical Review Letters</i>. American Physical Society.
    <a href="https://doi.org/10.1103/PhysRevLett.134.063601">https://doi.org/10.1103/PhysRevLett.134.063601</a>
  chicago: Redchenko, Elena, M. Zens, Martin Zemlicka, Matilda Peruzzo, Farid Hassani,
    Riya Sett, Przemyslaw D Zielinski, et al. “Observation of Collapse and Revival
    in a Superconducting Atomic Frequency Comb.” <i>Physical Review Letters</i>. American
    Physical Society, 2025. <a href="https://doi.org/10.1103/PhysRevLett.134.063601">https://doi.org/10.1103/PhysRevLett.134.063601</a>.
  ieee: E. Redchenko <i>et al.</i>, “Observation of collapse and revival in a superconducting
    atomic frequency comb,” <i>Physical Review Letters</i>, vol. 134, no. 6. American
    Physical Society, 2025.
  ista: Redchenko E, Zens M, Zemlicka M, Peruzzo M, Hassani F, Sett R, Zielinski PD,
    Dhar HS, Krimer DO, Rotter S, Fink JM. 2025. Observation of collapse and revival
    in a superconducting atomic frequency comb. Physical Review Letters. 134(6), 063601.
  mla: Redchenko, Elena, et al. “Observation of Collapse and Revival in a Superconducting
    Atomic Frequency Comb.” <i>Physical Review Letters</i>, vol. 134, no. 6, 063601,
    American Physical Society, 2025, doi:<a href="https://doi.org/10.1103/PhysRevLett.134.063601">10.1103/PhysRevLett.134.063601</a>.
  short: E. Redchenko, M. Zens, M. Zemlicka, M. Peruzzo, F. Hassani, R. Sett, P.D.
    Zielinski, H.S. Dhar, D.O. Krimer, S. Rotter, J.M. Fink, Physical Review Letters
    134 (2025).
corr_author: '1'
date_created: 2025-03-02T23:01:52Z
date_published: 2025-02-14T00:00:00Z
date_updated: 2026-11-04T23:31:12Z
day: '14'
ddc:
- '530'
department:
- _id: JoFi
doi: 10.1103/PhysRevLett.134.063601
ec_funded: 1
external_id:
  arxiv:
  - '2310.04200'
  isi:
  - '001454696700003'
  pmid:
  - '40021171'
file:
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  file_size: 2080408
  relation: main_file
  success: 1
file_date_updated: 2025-03-04T10:40:50Z
fulldoi: https://doi.org/10.1103/PhysRevLett.134.063601
has_accepted_license: '1'
intvolume: '       134'
isi: 1
issue: '6'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: bdb108fd-d553-11ed-ba76-83dc74a9864f
  grant_number: F07105
  name: QUANTUM INFORMATION SYSTEMS BEYOND CLASSICAL CAPABILITIES / P5- Integration
    of Superconducting Quantum Circuits
- _id: 26336814-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '758053'
  name: A Fiber Optic Transceiver for Superconducting Qubits
- _id: 26B354CA-B435-11E9-9278-68D0E5697425
  name: Controllable Collective States of Superconducting Qubit Ensembles
publication: Physical Review Letters
publication_identifier:
  eissn:
  - 1079-7114
  issn:
  - 0031-9007
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
related_material:
  record:
  - id: '19533'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Observation of collapse and revival in a superconducting atomic frequency comb
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: 134
year: '2025'
...
---
OA_place: publisher
_id: '20212'
abstract:
- lang: eng
  text: "Cortical development has been studied for many decades and with each passing
    year, we learn \r\nmore about the processes that govern the tightly regulated
    developmental program. Up until \r\nrecently, the field has struggled to gain
    reliable access to progenitors at the single-cell level, \r\nlimiting the resolution
    at which we can study cortical development in vivo. Therefore, much of \r\nthe
    data we have on mammalian cortical development is at the cell population level.
    The \r\nsubsequent pages of this thesis describe novel elements of cortical development
    in mice; \r\nacquired using a candidate gene approach in conjunction with Mosaic
    Analysis with Double \r\nMarkers (MADM) to achieve single cell resolution. In
    this thesis, I briefly provide an overview \r\nof the state of the field, describe
    the methodology used to quantify morphological \r\ncharacteristics of neurons
    and glia, and delve into the role of Phosphatase and tensin \r\nhomologue on chromosome
    ten (Pten) in neurogenesis and gliogenesis in the developing mouse \r\ncortex.
    By using MADM to generate genetic mosaics, in which only a small fraction of cells
    \r\nare mutated, to study population-level changes, we can bypass the early postnatal
    lethality \r\nreported in Pten conditional knockouts (cKOs) using Emx1-Cre. We
    used Emx1-CreERT2 to \r\ninduce clonal deletion of Pten, and quantify RGP neurogenic
    output at the single progenitor \r\nlevel. Pten-mutant neuron populations within
    the mosaics were significantly expanded. In the \r\nlatter parts of this thesis,
    we describe how Pten deletion leads to an increase in the abundance \r\nof astrocytes.
    We availed ourselves of the flexibility offered by the MADM system to generate
    \r\nPten mosaics within a series of distinct knockout tissues to test for the
    interactions between \r\nPten and a battery of genes involved in distinct pro-gliogenic
    signaling pathways. Our survey \r\nof Pten’s interactions with genes in key signaling
    pathways reveals that ERK1/2 are the critical \r\neffectors downstream of EGFR
    signaling essential for gliogenesis. Altogether, our results \r\ndemonstrate that
    Pten plays critical and distinct roles throughout cortical RGP lineage \r\nprogression. "
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "I would also like to\r\nthank the Austrian Academy of Sciences for
  awarding me a 2-year DOC fellowship\r\n(DOC26253)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Osvaldo
  full_name: Miranda, Osvaldo
  id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
  last_name: Miranda
  orcid: 0000-0001-6618-6889
citation:
  ama: Miranda O. Unraveling the role of Pten in cortical stem cell lineage progression
    using MADM. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20212">10.15479/AT-ISTA-20212</a>
  apa: Miranda, O. (2025). <i>Unraveling the role of Pten in cortical stem cell lineage
    progression using MADM</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20212">https://doi.org/10.15479/AT-ISTA-20212</a>
  chicago: Miranda, Osvaldo. “Unraveling the Role of Pten in Cortical Stem Cell Lineage
    Progression Using MADM.” Institute of Science and Technology Austria, 2025. <a
    href="https://doi.org/10.15479/AT-ISTA-20212">https://doi.org/10.15479/AT-ISTA-20212</a>.
  ieee: O. Miranda, “Unraveling the role of Pten in cortical stem cell lineage progression
    using MADM,” Institute of Science and Technology Austria, 2025.
  ista: Miranda O. 2025. Unraveling the role of Pten in cortical stem cell lineage
    progression using MADM. Institute of Science and Technology Austria.
  mla: Miranda, Osvaldo. <i>Unraveling the Role of Pten in Cortical Stem Cell Lineage
    Progression Using MADM</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-20212">10.15479/AT-ISTA-20212</a>.
  short: O. Miranda, Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression
    Using MADM, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-22T14:07:00Z
date_published: 2025-08-22T00:00:00Z
date_updated: 2026-10-02T12:16:56Z
day: '22'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/AT-ISTA-20212
doi_confirm: '1'
file:
- access_level: closed
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  creator: omiranda
  date_created: 2025-08-26T09:03:50Z
  date_updated: 2026-08-26T22:30:02Z
  embargo_to: open_access
  file_id: '20230'
  file_name: 2025_MirandaRomero_OsvaldoAntonio_Thesis.docx
  file_size: 32887334
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  date_created: 2025-08-26T09:05:55Z
  date_updated: 2026-08-26T22:30:02Z
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  relation: main_file
file_date_updated: 2026-08-26T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20212
has_accepted_license: '1'
keyword:
- Pten
- mtor
- cortical development
- MADM
- Mapk
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '119'
project:
- _id: 34c9fbcb-11ca-11ed-8bc3-98fa5658610d
  grant_number: '26253'
  name: Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression
    and Astrocyte Development
publication_identifier:
  isbn:
  - 978-3-99078-063-3
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '17425'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
title: Unraveling the role of Pten in cortical stem cell lineage progression using
  MADM
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: publisher
_id: '20117'
abstract:
- lang: eng
  text: "Auxin is essential for many aspects of plant growth and development, from
    \r\nembryogenesis to organ senescence. Polar auxin transport leads to local auxin
    maxima and \r\ngradients, which are important for regulating various plant development
    process, including \r\nembryogenesis, organogenesis and vascular tissue formation.
    The polar auxin transport is \r\nmediated by auxin influx carrier AUX1/LAX proteins
    and efflux carrier PIN proteins. The \r\nregulation of PIN proteins is a key convergence
    of crosstalk between auxin and other \r\nhormones, such as cytokinin. Cytokinin
    promotes the degradation of PIN1 in Arabidopsis \r\nroots, preferentially the
    dephosphorylated PIN1, and the process is independent of \r\ntranscription and
    translation (Marhavý et al., 2011; Marhavý et al., 2014). The internalization
    \r\nof PIN proteins from plasma membrane is controlled by clathrin-mediated endocytosis
    \r\n(Dhonukshe et al., 2007; Kitakura et al., 2011). However, whether cytokinin
    affects the PIN1 \r\ndegradation through regulating the phosphorylation of PIN1
    or trafficking components is \r\nunknown. Here, we demonstrate that dynamin related
    protein DRP2s are required for the \r\ncytokinin regulated trafficking of PIN1
    and PIN2 in Arabidopsis root epidermal cells. Despite \r\nthe reported redundancy
    of DRP2A and DRP2B in gametophyte development, we found that \r\nCK-mediated PIN1
    degradation and –induced PIN2 membrane localization is affected in drp2a \r\nor
    drp2b single mutants. Interestingly, we found that cytokinin regulates the recruitment
    of \r\nDRP2A—but not DRP2B—to clathrin-coated pits, and affects the stability
    and plasma \r\nmembrane localization of DRP2A. Furthermore, we studied the involvement
    of cytokinin \r\nreceptors in the regulation of cytokinin on DRP2A. Additionally,
    the assembly and disassembly \r\ncycle of dynamin is mediated by its dephosphorylation
    and phosphotylation cycle; thus, we \r\ninvestigated the role of DRP2A phosphorylation
    in its cytokinin-regulated assembly and in \r\ncytokinin-regulated PIN trafficking.
    Altogether, we found that cytokinin regulated PIN \r\ntrafficking in Arabidopsis
    root epidermal cells involves modulation of the phosphorylation of \r\nendocytosis
    accessory protein DRP2A. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "I would also like to acknowledge the invaluable assistance provided
  by the Plant\r\nFacility, Imaging & Optics Facility, and the Lab Support Facility.
  The technical support and\r\nresources offered by these facilities were indispensable
  to the successful completion of my\r\nexperiments."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Yiqun
  full_name: Wang, Yiqun
  id: 82F537F2-B517-11E9-84D7-6433E6697425
  last_name: Wang
citation:
  ama: Wang Y. The role of dynamin related protein 2A in cytokinin regulated plant
    growth and development. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20117">10.15479/AT-ISTA-20117</a>
  apa: Wang, Y. (2025). <i>The role of dynamin related protein 2A in cytokinin regulated
    plant growth and development</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT-ISTA-20117">https://doi.org/10.15479/AT-ISTA-20117</a>
  chicago: Wang, Yiqun. “The Role of Dynamin Related Protein 2A in Cytokinin Regulated
    Plant Growth and Development.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-20117">https://doi.org/10.15479/AT-ISTA-20117</a>.
  ieee: Y. Wang, “The role of dynamin related protein 2A in cytokinin regulated plant
    growth and development,” Institute of Science and Technology Austria, 2025.
  ista: Wang Y. 2025. The role of dynamin related protein 2A in cytokinin regulated
    plant growth and development. Institute of Science and Technology Austria.
  mla: Wang, Yiqun. <i>The Role of Dynamin Related Protein 2A in Cytokinin Regulated
    Plant Growth and Development</i>. Institute of Science and Technology Austria,
    2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20117">10.15479/AT-ISTA-20117</a>.
  short: Y. Wang, The Role of Dynamin Related Protein 2A in Cytokinin Regulated Plant
    Growth and Development, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-04T15:24:21Z
date_published: 2025-08-04T00:00:00Z
date_updated: 2026-10-02T12:33:36Z
day: '04'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: EvBe
doi: 10.15479/AT-ISTA-20117
doi_confirm: '1'
file:
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  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: yiqwang
  date_created: 2025-08-22T08:22:10Z
  date_updated: 2026-09-03T22:30:03Z
  embargo_to: open_access
  file_id: '20209'
  file_name: 2025_Wang_Yiqun_Thesis.docx
  file_size: 25798848
  relation: source_file
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  checksum: 8d7a2383f66377da675d379ec30ea0fe
  content_type: application/pdf
  creator: yiqwang
  date_created: 2025-08-22T10:32:30Z
  date_updated: 2026-09-03T22:30:03Z
  embargo: 2026-09-03
  file_id: '20211'
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  relation: main_file
file_date_updated: 2026-09-03T22:30:03Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20117
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '108'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '18063'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
title: The role of dynamin related protein 2A in cytokinin regulated plant growth
  and development
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20187'
abstract:
- lang: eng
  text: Very long-chain fatty acids (VLCFAs), being constituents of different types
    of lipids, are critical factors in plant development, presumably due to their
    impact on the endomembrane system. The VLCFAs are synthesized in the endoplasmic
    reticulum by a heterotetrameric enzymatic complex including β-ketoacyl CoA reductase
    1 (KCR1), whose mutant is lethal. Here, we describe the ectopic shoot meristems
    (esm) mutant, a viable kcr1 allele presumably affecting surface properties of
    the KCR1 protein. This kcr1-2 mutant shows reduced fatty acyl elongation that
    impacts VLCFAs. The kcr1-2 plants show severe defects during different stages
    of development, which all correlate with defects in polar localization and subcellular
    trafficking of PIN auxin transporters and resulting asymmetric auxin distribution.
    Detailed analysis of KCR1 expression and patterning defects in kcr1-2 suggests
    that KCR1 plays a role in delineating boundaries around meristematic and specialized
    differentiating tissues, including root and shoot meristems, initiating lateral
    roots, lateral root primordia, and trichomes. In these contexts, KCR1-produced
    VLCFAs may act in a non-cell-autonomous manner. Viable kcr1-2 represents a useful
    tool to study VLCFA roles in plant development and highlights VLCFAs as critical
    developmental factors at the interface of cell polarity and tissue development.
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: LifeSc
acknowledgement: "We gratefully acknowledge the Imaging and Optics, Electron Microscopy
  (especially Vanessa Zheden for technical assistance) and Life Science (in particular
  Dorota Jaworska) facilities at ISTA for their continuous support. Authors would
  like to thank Michelle Gallei for advice during the generation of the transgenic
  lines; Zuzana Gelová for advice with DR5rev::GFP analyses; Ivan Kulich for help
  and advice on trichome imaging; Aline Monzer for generous help with hypocotyl and
  root analyses; Shutang Tan for help with the NGS data analysis; and Milan Župunski
  for advice on abiotic stress experiments. We would like to thank Dolf Weijers for
  the SOSEKI (SOK) marker line seeds. This work has benefited from the support of
  IJPB's Plant Observatory platforms P0-Chem.\r\n\r\nThis work was supported by Austrian
  Science Fund (FWF) (I 6123-B) and Science and Technology Department of Jiangxi Province
  (20223BCJ25037) to Huibin Han. The IJPB benefits from the support of Saclay Plant
  Sciences-SPS (ANR-17-EUR-0007)."
article_number: e70396
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: David
  full_name: Babic, David
  id: db566d23-f6e0-11ea-865d-e6f270e968e7
  last_name: Babic
- first_name: Rashed
  full_name: Abualia, Rashed
  id: 4827E134-F248-11E8-B48F-1D18A9856A87
  last_name: Abualia
  orcid: 0000-0002-9357-9415
- first_name: Lukas
  full_name: Fiedler, Lukas
  id: 7c417475-8972-11ed-ae7b-8b674ca26986
  last_name: Fiedler
- first_name: Linlin
  full_name: Qi, Linlin
  id: 44B04502-A9ED-11E9-B6FC-583AE6697425
  last_name: Qi
  orcid: 0000-0001-5187-8401
- first_name: Frédérique
  full_name: Tellier, Frédérique
  last_name: Tellier
- first_name: Adrijana
  full_name: Smoljan, Adrijana
  id: cced8a85-223e-11ed-af04-b0596c55053b
  last_name: Smoljan
- first_name: Hana
  full_name: Rakusova, Hana
  id: 4CAAA450-78D2-11EA-8E57-B40A396E08BA
  last_name: Rakusova
- first_name: Petr
  full_name: Valošek, Petr
  id: 3CDB6F94-F248-11E8-B48F-1D18A9856A87
  last_name: Valošek
- first_name: Huibin
  full_name: Han, Huibin
  id: 31435098-F248-11E8-B48F-1D18A9856A87
  last_name: Han
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jean Denis
  full_name: Faure, Jean Denis
  last_name: Faure
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Babic D, Abualia R, Fiedler L, et al. Biosynthesis of very long-chain fatty
    acids is required for Arabidopsis auxin-mediated embryonic and post-embryonic
    development. <i>Plant Journal</i>. 2025;123(3). doi:<a href="https://doi.org/10.1111/tpj.70396">10.1111/tpj.70396</a>
  apa: Babic, D., Abualia, R., Fiedler, L., Qi, L., Tellier, F., Smoljan, A., … Friml,
    J. (2025). Biosynthesis of very long-chain fatty acids is required for Arabidopsis
    auxin-mediated embryonic and post-embryonic development. <i>Plant Journal</i>.
    Wiley. <a href="https://doi.org/10.1111/tpj.70396">https://doi.org/10.1111/tpj.70396</a>
  chicago: Babic, David, Rashed Abualia, Lukas Fiedler, Linlin Qi, Frédérique Tellier,
    Adrijana Smoljan, Hana Rakusova, et al. “Biosynthesis of Very Long-Chain Fatty
    Acids Is Required for Arabidopsis Auxin-Mediated Embryonic and Post-Embryonic
    Development.” <i>Plant Journal</i>. Wiley, 2025. <a href="https://doi.org/10.1111/tpj.70396">https://doi.org/10.1111/tpj.70396</a>.
  ieee: D. Babic <i>et al.</i>, “Biosynthesis of very long-chain fatty acids is required
    for Arabidopsis auxin-mediated embryonic and post-embryonic development,” <i>Plant
    Journal</i>, vol. 123, no. 3. Wiley, 2025.
  ista: Babic D, Abualia R, Fiedler L, Qi L, Tellier F, Smoljan A, Rakusova H, Valošek
    P, Han H, Benková E, Faure JD, Friml J. 2025. Biosynthesis of very long-chain
    fatty acids is required for Arabidopsis auxin-mediated embryonic and post-embryonic
    development. Plant Journal. 123(3), e70396.
  mla: Babic, David, et al. “Biosynthesis of Very Long-Chain Fatty Acids Is Required
    for Arabidopsis Auxin-Mediated Embryonic and Post-Embryonic Development.” <i>Plant
    Journal</i>, vol. 123, no. 3, e70396, Wiley, 2025, doi:<a href="https://doi.org/10.1111/tpj.70396">10.1111/tpj.70396</a>.
  short: D. Babic, R. Abualia, L. Fiedler, L. Qi, F. Tellier, A. Smoljan, H. Rakusova,
    P. Valošek, H. Han, E. Benková, J.D. Faure, J. Friml, Plant Journal 123 (2025).
corr_author: '1'
date_created: 2025-08-17T22:01:36Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2026-11-04T23:31:15Z
day: '01'
ddc:
- '580'
department:
- _id: EvBe
- _id: JiFr
- _id: GradSch
doi: 10.1111/tpj.70396
external_id:
  isi:
  - '001547884300001'
  pmid:
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issue: '3'
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project:
- _id: bd76d395-d553-11ed-ba76-f678c14f9033
  grant_number: I06123
  name: Peptide receptors for auxin canalization in Arabidopsis
publication: Plant Journal
publication_identifier:
  eissn:
  - 1365-313X
  issn:
  - 0960-7412
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
  record:
  - id: '20362'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Biosynthesis of very long-chain fatty acids is required for Arabidopsis auxin-mediated
  embryonic and post-embryonic development
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 123
year: '2025'
...
---
OA_place: publisher
_id: '20362'
abstract:
- lang: eng
  text: "Arabidopsis embryo has long served as a model system for understanding how
    plant body \r\npatterning and axis establishment arise. Previous work established
    that auxin flows, directed \r\nby polar transport and reinforced by local biosynthesis,
    underpin axes formation, while recent \r\nstudies suggest that maternal tissue,
    membrane composition and surface receptor signaling add \r\nfurther regulatory
    layers. In this thesis, we dissect the layers of auxin-mediated processes which
    \r\nguide plant embryonic and post-embryonic development. We review methodological
    advances \r\nthat allow the embryo to be imaged and studied. These tools offer
    exciting venues for future \r\naddressing of outstanding research questions. Furthermore,
    we dissect the contribution of \r\nmaternal auxin for early embryo patterning.
    Targeted auxin scavenging in the integuments \r\nlowers the hormone reaching the
    proembryo, destabilizes PIN7 in the suspensor and weakens \r\nthe initial apical
    maximum. The resulting deficit dampens downstream embryonic auxin \r\nbiosynthesis,
    as well as auxin flow towards the root pole, indicating that maternally provided
    \r\nauxin controls auxin flows in the embryos on a larger scale than previously
    understood. \r\nIntriguingly, we uncover a prolonged maternal effect mediated
    by the receptor-like kinases \r\nTMK1 and TMK4. Reciprocal crosses and transgene
    analyses hint that these genes could be \r\npreferentially maternally-derived
    in both embryos and seedlings. Loss of maternal TMK \r\nactivity arrests embryos,
    affects seedling development and persists into adult growth, \r\nsuggesting that
    maternal effect could shape development beyond fertilization and early \r\nembryogenesis.
    Finally, we describe the role of very-long-chain fatty acids and membrane \r\ncomposition
    on PIN proteins and their auxin-induced relocalization. Disruption in this lipid
    \r\nmetabolism triggers widespread patterning errors. \r\nTogether, these results
    reposition early plant patterning as a hierarchical cascade that begins \r\nwith
    maternal auxin, gets amplified by auxin transport and biosynthesis, potentially
    modulated \r\nby maternal receptor signaling and could ultimately be gated by
    the biophysical properties of \r\nthe membrane. By integrating auxin supply, genetic
    imprinting and lipid-dependent trafficking \r\ninto a single narrative, this thesis
    helps shifting the approach of viewing the embryo as an \r\nautonomous unit to
    regarding it as a dynamic system, continuously sculpted by its maternal \r\ncontext."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: David
  full_name: Babic, David
  id: db566d23-f6e0-11ea-865d-e6f270e968e7
  last_name: Babic
citation:
  ama: Babic D. Mechanisms of auxin-mediated early embryogenesis in Arabidopsis thaliana.
    2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20362">10.15479/AT-ISTA-20362</a>
  apa: Babic, D. (2025). <i>Mechanisms of auxin-mediated early embryogenesis in Arabidopsis
    thaliana</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20362">https://doi.org/10.15479/AT-ISTA-20362</a>
  chicago: Babic, David. “Mechanisms of Auxin-Mediated Early Embryogenesis in Arabidopsis
    Thaliana.” Institute of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20362">https://doi.org/10.15479/AT-ISTA-20362</a>.
  ieee: D. Babic, “Mechanisms of auxin-mediated early embryogenesis in Arabidopsis
    thaliana,” Institute of Science and Technology Austria, 2025.
  ista: Babic D. 2025. Mechanisms of auxin-mediated early embryogenesis in Arabidopsis
    thaliana. Institute of Science and Technology Austria.
  mla: Babic, David. <i>Mechanisms of Auxin-Mediated Early Embryogenesis in Arabidopsis
    Thaliana</i>. Institute of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20362">10.15479/AT-ISTA-20362</a>.
  short: D. Babic, Mechanisms of Auxin-Mediated Early Embryogenesis in Arabidopsis
    Thaliana, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-09-17T13:28:01Z
date_published: 2025-09-18T00:00:00Z
date_updated: 2026-10-16T07:59:32Z
day: '18'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JiFr
- _id: EvBe
doi: 10.15479/AT-ISTA-20362
doi_confirm: '1'
file:
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  date_updated: 2026-09-25T22:30:02Z
  embargo: 2026-09-25
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  file_name: 2025_David_Babic_Thesis.pdf
  file_size: 7501548
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  creator: dbabic
  date_created: 2025-09-24T13:43:14Z
  date_updated: 2026-09-25T22:30:02Z
  embargo_to: open_access
  file_id: '20389'
  file_name: Thesis_Babic_draft.docx
  file_size: 23206052
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file_date_updated: 2026-09-25T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20362
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '116'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '20187'
    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
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
title: Mechanisms of auxin-mediated early embryogenesis in Arabidopsis thaliana
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: repository
_id: '21427'
abstract:
- lang: eng
  text: While tumor malignancy has been extensively studied under the prism of genetic
    and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal
    interactions with the microenvironment. This raises the hitherto untested possibility
    that heterogeneity of the untransformed tumor stroma can actively fuel malignant
    progression. As biological heterogeneity is inherently difficult to control, we
    adopted a reductionist approach and let tumor cells invade micro-engineered environments
    harboring obstacles with precision-controlled geometry. We find that not only
    the presence of obstacles, but more surprisingly their spatial disorder, causes
    a drastic shift from a collective to a single-cell mode of invasion – comparable
    in strength to cadherin loss. Combining live-imaging and perturbation experiments
    with minimal biophysical modeling, we demonstrate that cell detachments result
    both from local geometrical constraints and a global integration of spatial disorder
    over time. We show that different types of microenvironments map onto different
    universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang
    (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with
    quenched disorder (KPZq). Our findings highlight generic physical principles for
    how the mode of cancer cell invasion depends on environmental heterogeneity, with
    potential implications to understand tumor evolution in vivo.
acknowledgement: "European Research Council, https://ror.org/0472cxd90, 101071793\r\nAustrian
  Academy of Sciences, 26360"
article_processing_charge: No
author:
- first_name: Zuzana
  full_name: Dunajova, Zuzana
  id: 4B39F286-F248-11E8-B48F-1D18A9856A87
  last_name: Dunajova
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Juraj
  full_name: Majek, Juraj
  id: 3e6d9473-f38e-11ec-8ae0-c4e05a8aa9e1
  last_name: Majek
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Erik
  full_name: Sahai, Erik
  last_name: Sahai
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Dunajova Z, Tasciyan S, Majek J, et al. Substrate heterogeneity promotes cancer
    cell dissemination through interface roughening. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>
  apa: Dunajova, Z., Tasciyan, S., Majek, J., Merrin, J., Sahai, E., Sixt, M. K.,
    &#38; Hannezo, E. B. (n.d.). Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2025.05.20.655037">https://doi.org/10.1101/2025.05.20.655037</a>
  chicago: Dunajova, Zuzana, Saren Tasciyan, Juraj Majek, Jack Merrin, Erik Sahai,
    Michael K Sixt, and Edouard B Hannezo. “Substrate Heterogeneity Promotes Cancer
    Cell Dissemination through Interface Roughening.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2025.05.20.655037">https://doi.org/10.1101/2025.05.20.655037</a>.
  ieee: Z. Dunajova <i>et al.</i>, “Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening,” <i>bioRxiv</i>. .
  ista: Dunajova Z, Tasciyan S, Majek J, Merrin J, Sahai E, Sixt MK, Hannezo EB. Substrate
    heterogeneity promotes cancer cell dissemination through interface roughening.
    bioRxiv, <a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>.
  mla: Dunajova, Zuzana, et al. “Substrate Heterogeneity Promotes Cancer Cell Dissemination
    through Interface Roughening.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>.
  short: Z. Dunajova, S. Tasciyan, J. Majek, J. Merrin, E. Sahai, M.K. Sixt, E.B.
    Hannezo, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2026-03-11T08:40:06Z
date_published: 2025-09-25T00:00:00Z
date_updated: 2026-11-04T23:31:15Z
day: '25'
ddc:
- '539'
- '570'
department:
- _id: GradSch
- _id: EdHa
- _id: MiSi
- _id: NanoFab
- _id: AnSa
doi: 10.1101/2025.05.20.655037
fulldoi: https://doi.org/10.1101/2025.05.20.655037
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2025.05.20.655037
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
  grant_number: '101071793'
  name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
    pushing forces'
- _id: 34d75525-11ca-11ed-8bc3-89b6307fee9d
  grant_number: '26360'
  name: Motile active matter models of migrating cells and chiral filaments
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '21439'
    relation: research_data
    status: public
  - id: '22963'
    relation: later_version
    status: public
  - id: '21423'
    relation: dissertation_contains
    status: public
status: public
title: Substrate heterogeneity promotes cancer cell dissemination through interface
  roughening
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '20393'
abstract:
- lang: eng
  text: "During vertebrate development, the morphogen Sonic Hedgehog (Shh) plays a
    key role in \r\npatterning the tissues of the extending body. This requires precise
    coordination between the \r\nsize of the source of Shh production and the embryo
    body. Shh is produced by the notochord, \r\nas well as floorplate of the neural
    tube. In this thesis, we investigated how the sizes of the \r\nnotochord and floorplate
    are regulated and how they impact the developing mouse embryo.  \r\nTo measure
    the size and shape of the developing mouse notochord and the cell behaviours \r\nwithin
    this organ, we performed high-resolution measurements in cleared embryos between
    \r\nE8.5 and E10.5 of development. Strikingly, our data revealed that the notochord
    maintains a \r\nconstant cross-sectional area throughout the trunk over time as
    it lengthens by cell \r\nproliferation. We show that this is achieved by a feedback
    between the notochord cell \r\nproliferation rate and both the cross-sectional
    area of the trunk notochord and elongation of \r\nthe embryo. Using live imaging,
    we further show that notochord cells undergo posteriorly\r\ndirected active cell
    migration and that this cell migration contributes to maintaining the \r\nstructural
    integrity of the notochord. Our results show a complex coordination of cell \r\nbehaviours
    that allow for robust notochord morphogenesis during mouse development and \r\nthe
    maintenance of a defined Shh source size.  \r\nShh produced by the notochord induces
    a secondary Shh-producing domain, the floor plate. \r\nHow the notochord and floor
    plate contribute to the formation of the Shh gradient in the \r\nneural tube and
    to the regulation of the floor plate size is poorly understood. Our theoretical
    \r\nand experimental analysis indicates that only the initial levels of notochord-derived
    Shh \r\ninfluence the size of the floor plate, and the floor plate is insensitive
    to its own production of \r\nShh. After its initial establishment, the floor plate
    expands by tissue growth, leading to scaling \r\nof the Shh gradient amplitude
    with tissue size.   \r\nAltogether, we show that the mechanisms regulating the
    sizes of the notochord and \r\nfloorplate in mouse development help to achieve
    size robustness of these tissues. Our data \r\ndemonstrate that the initial establishment
    of the Shh gradient in the neural tube is strongly \r\ndependent on the notochord
    and suggest that the robustness of notochord morphogenesis \r\nis essential for
    pattern formation. Later in development, the floor plate size and the Shh \r\ngradient
    are coupled to neural tube growth. Our findings provide new insights on how pattern
    \r\nformation, tissue growth and morphogenesis interact to ensure reproducible
    developmental \r\noutcomes. "
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
  orcid: 0000-0001-6060-4795
citation:
  ama: Kishi K. Regulation of notochord and floor plate size during mouse development.
    2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20393">10.15479/AT-ISTA-20393</a>
  apa: Kishi, K. (2025). <i>Regulation of notochord and floor plate size during mouse
    development</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20393">https://doi.org/10.15479/AT-ISTA-20393</a>
  chicago: Kishi, Kasumi. “Regulation of Notochord and Floor Plate Size during Mouse
    Development.” Institute of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20393">https://doi.org/10.15479/AT-ISTA-20393</a>.
  ieee: K. Kishi, “Regulation of notochord and floor plate size during mouse development,”
    Institute of Science and Technology Austria, 2025.
  ista: Kishi K. 2025. Regulation of notochord and floor plate size during mouse development.
    Institute of Science and Technology Austria.
  mla: Kishi, Kasumi. <i>Regulation of Notochord and Floor Plate Size during Mouse
    Development</i>. Institute of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20393">10.15479/AT-ISTA-20393</a>.
  short: K. Kishi, Regulation of Notochord and Floor Plate Size during Mouse Development,
    Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-09-25T10:08:10Z
date_published: 2025-09-24T00:00:00Z
date_updated: 2026-10-16T08:31:16Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: AnKi
- _id: EdHa
doi: 10.15479/AT-ISTA-20393
doi_confirm: '1'
file:
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fulldoi: https://doi.org/10.15479/AT-ISTA-20393
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '102'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '18481'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
title: Regulation of notochord and floor plate size during mouse development
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: publisher
_id: '20364'
abstract:
- lang: eng
  text: "Auxin is a central regulator of plant growth and development, orchestrating
    processes from \r\nembryogenesis to senescence through a complex network of biosynthesis,
    transport, and \r\nsignaling pathways.  \r\nIn Arabidopsis thaliana, canonical
    nuclear auxin signaling is mediated by the TIR1/AFB \r\nreceptors, which promote
    degradation of AUX/IAA repressors to enable ARF transcription \r\nfactors-driven
    transcriptional reprogramming. Parallel to this well-established nuclear \r\nmechanism,
    auxin also triggers rapid, non-transcriptional responses. In particular, at the
    cell \r\nsurface, most notably through ABP1 and TMKs. Despite decades of research,
    the integration \r\nof these pathways and their links to fundamental cellular
    processes remains not fully \r\nunderstood.  \r\nIn this study, we uncover a new
    role for TIR1/AFB signaling in rapidly activating \r\nmacroautophagy during developmental
    reprogramming. Auxin induces autophagy via \r\nTIR1/AFB adenylate cyclase activity,
    linking auxin perception to cAMP production and \r\ntranscriptional activation
    of autophagy machinery. Autophagy-deficient mutants exhibit \r\ndelayed meristem
    differentiation, impaired lateral root progression, and reduced shoot \r\norganogenesis,
    demonstrating its necessity for timely developmental transitions. \r\nWe also
    revisit the ABP1-TMK1 cell-surface auxin perception complex, providing \r\nbiochemical
    and mass photometry evidence for auxin-dependent complex formation. We show \r\nthat
    ABP1-TMK1 triggers an ultrafast global phosphorylation response targeting ~1000
    \r\nproteins, including the auxin transporter PIN2, and Rho-of-plants (ROP) GTPases
    regulators. \r\nThis pathway directly regulates PIN2 phosphorylation, for gravitropism
    and auxin dependent \r\nROP activation. \r\nThese findings establish an integrated
    framework in which nuclear TIR1/AFB signaling and \r\ncell-surface ABP1-TMK signaling
    act in parallel to synchronize gene expression, cytoplasmic \r\nremodelling, and
    transporter regulation, thereby ensuring robust developmental plasticity in \r\nArabidopsis
    thaliana. "
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: "Plant Facility,\r\nProtein Service Facility"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Caterina
  full_name: Giannini, Caterina
  id: e3fdddd5-f6e0-11ea-865d-ca99ee6367f4
  last_name: Giannini
citation:
  ama: Giannini C. Nuclear and cell surface auxin signaling in A. thaliana developmental
    transitions. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20364">10.15479/AT-ISTA-20364</a>
  apa: Giannini, C. (2025). <i>Nuclear and cell surface auxin signaling in A. thaliana
    developmental transitions</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT-ISTA-20364">https://doi.org/10.15479/AT-ISTA-20364</a>
  chicago: Giannini, Caterina. “Nuclear and Cell Surface Auxin Signaling in A. Thaliana
    Developmental Transitions.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-20364">https://doi.org/10.15479/AT-ISTA-20364</a>.
  ieee: C. Giannini, “Nuclear and cell surface auxin signaling in A. thaliana developmental
    transitions,” Institute of Science and Technology Austria, 2025.
  ista: Giannini C. 2025. Nuclear and cell surface auxin signaling in A. thaliana
    developmental transitions. Institute of Science and Technology Austria.
  mla: Giannini, Caterina. <i>Nuclear and Cell Surface Auxin Signaling in A. Thaliana
    Developmental Transitions</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-20364">10.15479/AT-ISTA-20364</a>.
  short: C. Giannini, Nuclear and Cell Surface Auxin Signaling in A. Thaliana Developmental
    Transitions, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-09-19T12:23:38Z
date_published: 2025-09-19T00:00:00Z
date_updated: 2026-10-16T08:24:09Z
day: '19'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JiFr
- _id: MaLo
doi: 10.15479/AT-ISTA-20364
doi_confirm: '1'
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file_date_updated: 2026-09-30T22:30:03Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20364
has_accepted_license: '1'
keyword:
- Auxin Signaling
- Plant Development
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '151'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12291'
    relation: part_of_dissertation
    status: public
  - id: '19399'
    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: Nuclear and cell surface auxin signaling in A. thaliana developmental transitions
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: repository
OA_type: green
_id: '19399'
abstract:
- lang: eng
  text: Phytohormone auxin and its directional transport mediate much of the remarkably
    plastic development of higher plants. Positive feedback between auxin signaling
    and transport is a key prerequisite for (i) self-organizing processes including
    vascular tissue formation and (ii) directional growth responses such as gravitropism.
    Here we identify a mechanism, by which auxin signaling directly targets PIN auxin
    transporters. Via the cell-surface ABP1-TMK1 receptor module, auxin rapidly induces
    phosphorylation and thus stabilization of PIN2. Following gravistimulation, initial
    auxin asymmetry activates autophosphorylation of the TMK1 kinase. This induces
    TMK1 interaction with and phosphorylation of PIN2, stabilizing PIN2 at the lower
    root side, thus reinforcing asymmetric auxin flow for root bending. Upstream of
    TMK1 in this regulation, ABP1 acts redundantly with the root-expressed ABP1-LIKE
    auxin receptor ABL3. Such positive feedback between cell-surface auxin signaling
    and PIN-mediated polar auxin transport is fundamental for robust root gravitropism
    and presumably also for other self-organizing developmental phenomena.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'We thank W. Gray for providing material; N. Gnyliukh and E. Cervenova
  for help with manuscript preparation; J. Schmid for help with cloning. We thank
  Dolf Weijers, Mark Roosjen, and Andre Kuhn for discussions and support with phospho-proteomic
  analyses. We thank the Bioimaging and Life Science facilities at ISTA for their
  excellent service and assistance. The research leading to these results has received
  funding from the European Research Council (ERC) under the European Union’s Horizon
  2020 research and innovation program grant agreement No 742985 and Austrian Science
  Fund (FWF): I3630-775 B25 to J.F; National Natural Science Foundation of China (Grant
  32130010, 31422008), start-up funds from FAFU to T.X., Y.J. was funded by ERC no.
  3363360-APPL under FP/2007-2013. L.R. was supported by FP7-PEOPLE-2011-COFUND ISTFELLOW
  program (IC1023FELL01) and the European Molecular Biology Organization (EMBO) long-term
  postdoctoral fellowship (ALTF 985- 2016). S.T. was supported by the National Natural
  Science Foundation of China (32321001).'
article_processing_charge: No
author:
- first_name: Lesia
  full_name: Rodriguez Solovey, Lesia
  id: 3922B506-F248-11E8-B48F-1D18A9856A87
  last_name: Rodriguez Solovey
  orcid: 0000-0002-7244-7237
- first_name: Lukas
  full_name: Fiedler, Lukas
  id: 7c417475-8972-11ed-ae7b-8b674ca26986
  last_name: Fiedler
- first_name: Minxia
  full_name: Zou, Minxia
  id: 5c243f41-03f3-11ec-841c-96faf48a7ef9
  last_name: Zou
- first_name: Caterina
  full_name: Giannini, Caterina
  id: e3fdddd5-f6e0-11ea-865d-ca99ee6367f4
  last_name: Giannini
- first_name: Aline
  full_name: Monzer, Aline
  id: 2DB5D88C-D7B3-11E9-B8FD-7907E6697425
  last_name: Monzer
- first_name: Dmitrii
  full_name: Vladimirtsev, Dmitrii
  id: 60466724-5355-11ee-ae5a-fa55e8f99c3d
  last_name: Vladimirtsev
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Yongfan
  full_name: Yu, Yongfan
  last_name: Yu
- first_name: Zuzana
  full_name: Gelová, Zuzana
  id: 0AE74790-0E0B-11E9-ABC7-1ACFE5697425
  last_name: Gelová
  orcid: 0000-0003-4783-1752
- first_name: Inge
  full_name: Verstraeten, Inge
  id: 362BF7FE-F248-11E8-B48F-1D18A9856A87
  last_name: Verstraeten
  orcid: 0000-0001-7241-2328
- first_name: Jakub
  full_name: Hajny, Jakub
  id: 4800CC20-F248-11E8-B48F-1D18A9856A87
  last_name: Hajny
  orcid: 0000-0003-2140-7195
- first_name: Meng
  full_name: Chen, Meng
  last_name: Chen
- first_name: Shutang
  full_name: Tan, Shutang
  id: 2DE75584-F248-11E8-B48F-1D18A9856A87
  last_name: Tan
  orcid: 0000-0002-0471-8285
- first_name: Lukas
  full_name: Hörmayer, Lukas
  id: 2EEE7A2A-F248-11E8-B48F-1D18A9856A87
  last_name: Hörmayer
  orcid: 0000-0001-8295-2926
- first_name: Lanxin
  full_name: Li, Lanxin
  id: 367EF8FA-F248-11E8-B48F-1D18A9856A87
  last_name: Li
  orcid: 0000-0002-5607-272X
- first_name: Maria Mar
  full_name: Marques-Bueno, Maria Mar
  last_name: Marques-Bueno
- first_name: Zainab
  full_name: Quddoos, Zainab
  id: 32ff3c64-04a0-11f0-a50f-d0c45bfac466
  last_name: Quddoos
- first_name: Gergely
  full_name: Molnar, Gergely
  id: 34F1AF46-F248-11E8-B48F-1D18A9856A87
  last_name: Molnar
- first_name: Tongda
  full_name: Xu, Tongda
  last_name: Xu
- first_name: Ivan
  full_name: Kulich, Ivan
  id: 57a1567c-8314-11eb-9063-c9ddc3451a54
  last_name: Kulich
- first_name: Yvon
  full_name: Jaillais, Yvon
  last_name: Jaillais
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Rodriguez Solovey L, Fiedler L, Zou M, et al. ABP1/ABL3-TMK1 cell-surface auxin
    signaling directly targets PIN2-mediated auxin fluxes for root gravitropism. <i>bioRxiv</i>.
    doi:<a href="https://doi.org/10.1101/2022.11.30.518503">10.1101/2022.11.30.518503</a>
  apa: Rodriguez Solovey, L., Fiedler, L., Zou, M., Giannini, C., Monzer, A., Vladimirtsev,
    D., … Friml, J. (n.d.). ABP1/ABL3-TMK1 cell-surface auxin signaling directly targets
    PIN2-mediated auxin fluxes for root gravitropism. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2022.11.30.518503">https://doi.org/10.1101/2022.11.30.518503</a>
  chicago: Rodriguez Solovey, Lesia, Lukas Fiedler, Minxia Zou, Caterina Giannini,
    Aline Monzer, Dmitrii Vladimirtsev, Marek Randuch, et al. “ABP1/ABL3-TMK1 Cell-Surface
    Auxin Signaling Directly Targets PIN2-Mediated Auxin Fluxes for Root Gravitropism.”
    <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2022.11.30.518503">https://doi.org/10.1101/2022.11.30.518503</a>.
  ieee: L. Rodriguez Solovey <i>et al.</i>, “ABP1/ABL3-TMK1 cell-surface auxin signaling
    directly targets PIN2-mediated auxin fluxes for root gravitropism,” <i>bioRxiv</i>.
    .
  ista: Rodriguez Solovey L, Fiedler L, Zou M, Giannini C, Monzer A, Vladimirtsev
    D, Randuch M, Yu Y, Gelová Z, Verstraeten I, Hajny J, Chen M, Tan S, Hörmayer
    L, Li L, Marques-Bueno MM, Quddoos Z, Molnar G, Xu T, Kulich I, Jaillais Y, Friml
    J. ABP1/ABL3-TMK1 cell-surface auxin signaling directly targets PIN2-mediated
    auxin fluxes for root gravitropism. bioRxiv, <a href="https://doi.org/10.1101/2022.11.30.518503">10.1101/2022.11.30.518503</a>.
  mla: Rodriguez Solovey, Lesia, et al. “ABP1/ABL3-TMK1 Cell-Surface Auxin Signaling
    Directly Targets PIN2-Mediated Auxin Fluxes for Root Gravitropism.” <i>BioRxiv</i>,
    doi:<a href="https://doi.org/10.1101/2022.11.30.518503">10.1101/2022.11.30.518503</a>.
  short: L. Rodriguez Solovey, L. Fiedler, M. Zou, C. Giannini, A. Monzer, D. Vladimirtsev,
    M. Randuch, Y. Yu, Z. Gelová, I. Verstraeten, J. Hajny, M. Chen, S. Tan, L. Hörmayer,
    L. Li, M.M. Marques-Bueno, Z. Quddoos, G. Molnar, T. Xu, I. Kulich, Y. Jaillais,
    J. Friml, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2025-03-13T08:36:48Z
date_published: 2025-02-20T00:00:00Z
date_updated: 2026-11-04T23:31:16Z
day: '20'
ddc:
- '580'
department:
- _id: JiFr
- _id: XiFe
doi: 10.1101/2022.11.30.518503
ec_funded: 1
fulldoi: https://doi.org/10.1101/2022.11.30.518503
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.11.30.518503
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 26538374-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03630
  name: Molecular mechanisms of endocytic cargo recognition in plants
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 26060676-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 985-2016
  name: Cell surface receptor complexes for auxin signaling in plants
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '19395'
    relation: dissertation_contains
    status: public
  - id: '20656'
    relation: later_version
    status: public
  - id: '20364'
    relation: dissertation_contains
    status: public
status: public
title: ABP1/ABL3-TMK1 cell-surface auxin signaling directly targets PIN2-mediated
  auxin fluxes for root gravitropism
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '19763'
abstract:
- lang: eng
  text: "Pattern formation in developing organs is controlled by morphogens. These
    signalling\r\nmolecules form concentration gradients across tissues, thereby providing
    positional\r\ninformation that instructs the pattern of cell differentiation.
    Morphogen gradients are highly\r\ndynamic in space and time. Many factors such
    as morphogen production, spreading,\r\ndegradation, cellular rearrangements and
    others could contribute to changes in the gradient\r\nshape, yet how the spatiotemporal
    signalling dynamics arise in many systems is still unclear.\r\nWe studied the
    dynamics of morphogen signalling and tissue patterning in the developing\r\nvertebrate
    neural tube. In this system, neural crest, roof plate and distinct dorsal progenitor\r\nsubtypes
    are specified in a spatially and temporally ordered manner in response to dorsal-toventral
    gradients of BMP and WNT signalling activity. How the BMP and WNT gradients are\r\nestablished
    and interpreted to ensure ordered cell specification is poorly understood.\r\nTo
    address this question, we developed a 2D embryonic stem cell differentiation system
    that\r\ncaptures key features of dorsal neural tube development. In this system,
    differentiated\r\ncolonies display remarkable self-organised pattern formation
    in response to uniformly\r\napplied BMP ligand. We established a method of differentiating
    the colonies using\r\nmicrofabricated stencils, which allowed us to control the
    initial size and shape of colonies\r\nwithout confining cell migration and colony
    growth. This led to highly reproducible pattern\r\nformation that facilitates
    quantification.\r\nUsing this approach, we observed striking two-phase temporal
    dynamics of BMP signalling in\r\nour colonies: a BMP gradient rapidly forms from
    the periphery to the centre of colonies,\r\nsubsequently disappears and is re-established
    again in the second phase. By combining our\r\nquantitative data with a data-driven
    theoretical model, we uncovered a temporal relay\r\nmechanism that underlies this
    biphasic BMP signalling dynamics. The first signalling phase is\r\ncontrolled
    by fast tissue-autonomous negative feedback that restricts the duration of the\r\ninitial
    response to BMP. The early BMP activity gradient moreover controls the spatial\r\norganisation
    of the cell type pattern: the absence of a first phase results in disordered cell\r\ntype
    pattern. The second phase is controlled by slow positive regulation of BMP signalling
    by\r\nthe transcription factor LMX1A, a key regulator of roof plate identity.
    WNT promotes the\r\nsecond phase of BMP signalling via positive feedback on LMX1A.\r\nAltogether,
    the mechanism that we uncovered ensures the coupling of sequential\r\ndevelopmental
    events, making pattern formation spatially and temporally organised.\r\nFurthermore,
    this mechanism allows the BMP signalling pathway to be reused in different\r\ncontexts
    – first for the establishment of the neural plate border, and subsequently for
    dorsal\r\nneural progenitor patterning. Our study supports a general developmental
    principle in which\r\nmultiple morphogens interact with transcriptional networks
    resulting in complex\r\nspatiotemporal signalling dynamics that ultimately drive
    organised pattern formation."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
acknowledgement: "My work would also not have been possible without the Imaging and
  Optics, the Life Science\r\nand the Preclinical Facility of ISTA. Your support has
  facilitated my research substantially. I\r\nalso want to thank the Graduate School
  Office for their never-ending support and their sincere\r\neffort to improve the
  PhD programme of the ISTA even further.\r\nThis work was supported by the Gesellschaft
  für Forschungsförderung Niederösterreich\r\nm.b.H. fellowship (SC19-011). Thank
  you for recognizing the importance of this project."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stefanie
  full_name: Rus, Stefanie
  id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
  last_name: Rus
  orcid: 0000-0001-8703-1093
citation:
  ama: Rus S. Dynamics of morphogen signalling and cell fate decisions in the dorsal
    neural tube. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19763">10.15479/AT-ISTA-19763</a>
  apa: Rus, S. (2025). <i>Dynamics of morphogen signalling and cell fate decisions
    in the dorsal neural tube</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT-ISTA-19763">https://doi.org/10.15479/AT-ISTA-19763</a>
  chicago: Rus, Stefanie. “Dynamics of Morphogen Signalling and Cell Fate Decisions
    in the Dorsal Neural Tube.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-19763">https://doi.org/10.15479/AT-ISTA-19763</a>.
  ieee: S. Rus, “Dynamics of morphogen signalling and cell fate decisions in the dorsal
    neural tube,” Institute of Science and Technology Austria, 2025.
  ista: Rus S. 2025. Dynamics of morphogen signalling and cell fate decisions in the
    dorsal neural tube. Institute of Science and Technology Austria.
  mla: Rus, Stefanie. <i>Dynamics of Morphogen Signalling and Cell Fate Decisions
    in the Dorsal Neural Tube</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-19763">10.15479/AT-ISTA-19763</a>.
  short: S. Rus, Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal
    Neural Tube, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-05-30T09:14:58Z
date_published: 2025-05-29T00:00:00Z
date_updated: 2026-10-20T08:57:07Z
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ddc:
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degree_awarded: PhD
department:
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- _id: GradSch
doi: 10.15479/AT-ISTA-19763
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month: '05'
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  grant_number: SC19-011
  name: The regulatory logic of pattern formation in the vertebrate dorsal neural
    tube
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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supervisor:
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  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
title: Dynamics of morphogen signalling and cell fate decisions in the dorsal neural
  tube
tmp:
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  short: CC BY-NC-ND (4.0)
type: dissertation
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year: '2025'
...
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abstract:
- lang: eng
  text: Developing tissues interpret dynamic changes in morphogen activity to generate
    cell type diversity. To quantitatively study bone morphogenetic protein (BMP)
    signaling dynamics in the mouse neural tube, we developed an embryonic stem cell
    differentiation system tailored for growing tissues. Differentiating cells form
    striking self-organized patterns of dorsal neural tube cell types driven by sequential
    phases of BMP signaling that are observed both in vitro and in vivo. Data-driven
    biophysical modeling showed that these dynamics result from coupling fast negative
    feedback with slow positive regulation of signaling by the specification of an
    endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling
    in space, we identify a BMP signaling relay that operates in time. This mechanism
    allows for a rapid initial concentration-sensitive response that is robustly terminated,
    thereby regulating balanced sequential cell type generation. Our study provides
    an experimental and theoretical framework to understand how signaling dynamics
    are exploited in developing tissues.
acknowledgement: We thank A. Miller and N. Papalopulu for reagents and J. Briscoe
  for comments on the manuscript. Work in the A.K. lab is supported by ISTA; the European
  Research Council under Horizon Europe, grant 101044579; and the Austrian Science
  Fund (FWF), grant https://doi.org/10.55776/F78. S.L. is supported by Gesellschaft
  für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. D.B.B. was
  supported by the NOMIS foundation as a NOMIS Fellow and by an EMBO Postdoctoral
  Fellowship (ALTF 343-2022).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Stefanie
  full_name: Rus, Stefanie
  id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
  last_name: Rus
  orcid: 0000-0001-8703-1093
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
- first_name: Thomas
  full_name: Minchington, Thomas
  id: 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f
  last_name: Minchington
- first_name: Martina
  full_name: Greunz, Martina
  id: 48A59534-F248-11E8-B48F-1D18A9856A87
  last_name: Greunz
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
citation:
  ama: Rus S, Brückner D, Minchington T, et al. Self-organized pattern formation in
    the developing mouse neural tube by a temporal relay of BMP signaling. <i>Developmental
    Cell</i>. 2025;60(4):567-580. doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a>
  apa: Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E.
    B., &#38; Kicheva, A. (2025). Self-organized pattern formation in the developing
    mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>.
    Cell Press. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a>
  chicago: Rus, Stefanie, David Brückner, Thomas Minchington, Martina Greunz, Jack
    Merrin, Edouard B Hannezo, and Anna Kicheva. “Self-Organized Pattern Formation
    in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental
    Cell</i>. Cell Press, 2025. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a>.
  ieee: S. Rus <i>et al.</i>, “Self-organized pattern formation in the developing
    mouse neural tube by a temporal relay of BMP signaling,” <i>Developmental Cell</i>,
    vol. 60, no. 4. Cell Press, pp. 567–580, 2025.
  ista: Rus S, Brückner D, Minchington T, Greunz M, Merrin J, Hannezo EB, Kicheva
    A. 2025. Self-organized pattern formation in the developing mouse neural tube
    by a temporal relay of BMP signaling. Developmental Cell. 60(4), 567–580.
  mla: Rus, Stefanie, et al. “Self-Organized Pattern Formation in the Developing Mouse
    Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental Cell</i>,
    vol. 60, no. 4, Cell Press, 2025, pp. 567–80, doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a>.
  short: S. Rus, D. Brückner, T. Minchington, M. Greunz, J. Merrin, E.B. Hannezo,
    A. Kicheva, Developmental Cell 60 (2025) 567–580.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: RNA-seq data has been deposited at GEO and are publicly
  available as of the date of publication. Accession numbers are listed in the key
  resources table. Code for the quantification of fluorescence intensity (FI) profiles
  in differentiated cells on stencils, as well as for model simulations, is available
  on GitHub (https://github.com/dbrueckner/NeuralTubeColonies, https://doi.org/10.5281/zenodo.13335390
date_created: 2025-01-09T11:25:47Z
date_published: 2025-02-24T00:00:00Z
date_updated: 2026-11-04T23:31:17Z
day: '24'
ddc:
- '570'
department:
- _id: AnKi
- _id: EdHa
- _id: NanoFab
doi: 10.1016/j.devcel.2024.10.024
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project:
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  name: Mechanisms of tissue size regulation in spinal cord development
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  name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
    control of growth and pattern in the spinal cord
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publisher: Cell Press
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supplementarymaterial: yes
title: Self-organized pattern formation in the developing mouse neural tube by a temporal
  relay of BMP signaling
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type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 60
year: '2025'
...
---
OA_place: publisher
_id: '20694'
abstract:
- lang: eng
  text: "Understanding the mechanisms underlying speciation is a central aim of evolutionary
    biology.\r\nA persistent challenge in the field is to identify loci that contribute
    to reproductive isolation,\r\nwhile disentangling signals of selection from demography,
    linkage and intrinsic genomic\r\nfeatures. Traditional population genomic approaches
    that rely on site-based statistics in\r\narbitrary fixed windows face inherent
    limitations, as they conflate historical and\r\ncontemporary processes of divergence
    and overlook haplotype structure. Recent advances in\r\nwhole-genome sequencing
    and methods to infer ancestral recombination graphs (ARGs) now\r\noffer the opportunity
    to study genealogical relationships explicitly, revealing how lineages\r\ncoalesce
    and recombine through time. By directly analysing haplotype clustering by species\r\nor
    phenotype and their patterns of coalescence, ARG-based methods show promise for\r\ndiagnosing
    sweeps, identifying barrier loci maintained under divergent selection amid gene\r\nflow,
    and tracing their evolutionary history.\r\nIn this thesis, I explore the utility
    of genealogical approaches for studying species\r\ndivergence. In chapter 2, I
    propose a conceptual framework for defining haplotype blocks\r\nthrough the structure
    of the ARG, using simulations and empirical data to highlight how\r\ngenealogical
    processes generate rich and often overlooked haplotypic patterns.\r\nIn chapter
    3, I examine the genomic basis of a key evolutionary innovation in marine\r\nsnails
    Littorina. These snails offer a unique opportunity to study an innovation because
    they\r\ninclude a very recent transition from egg-laying to live bearing, yet
    snails with the different\r\nreproductive modes are not reciprocally monophyletic.
    I exploited this by using topology\r\nclustering in ARG-derived local genealogical
    trees to pinpoint narrow genomic regions or\r\nhaplotype blocks that carry swept
    alleles, thus revealing that the transition from egg-laying\r\nto live-bearing
    involves multiple, live-bearer-specific sweeps.\r\nChapter 4 establishes a population-scale,
    phased genomic resource for Antirrhinum\r\nmajus, using cost-effective haplotagging,
    then optimizes imputation from low-coverage data\r\nagainst high-accuracy KASP
    sequencing to maximize sequence completeness with modest\r\naccuracy trade-offs
    against a traditional short-read sequence pipeline. A hybrid phasing\r\nstrategy
    combines molecular phasing with statistical phasing to generate phased whole\r\ngenome
    sequences of 1084 Antirrhinum individuals at a fraction of long-read sequencing\r\ncosts.\r\nIn
    chapter 5, I analyse hybridising populations from two replicate hybrid zones to
    find\r\na parallel genetic basis of flower colour, amidst the noise in genomic
    differentiation landscape\r\ndriven by variation in demographic history. While
    outlier genome scans of FST failed to dissect\r\nthe causes of differentiation,
    ARG-based topology clustering revealed a reuse of colour\r\nassociated haplotypes
    across hybrid zones. In addition to the biological insight, this chapter\r\nalso
    presents a comparison of the latest ARG inference tools, showing that signals
    of\r\nAbstract\r\nviii\r\ntopological clustering qualitatively agree between methods,
    despite differences in the tree\r\nsequences.\r\nNext, in chapter 6, by leveraging
    ~1000 individuals in one of the hybrid zones, I\r\nintegrated genome-wide association
    studies of floral pigmentation with genealogical\r\ninference, to test for additional
    colour loci, and confirm the effect of previously described loci.\r\nThis work
    demonstrates that flower colour variation is driven by a small number of large
    effect\r\nloci, while also hinting at the presence of a new candidate regulatory
    factor.\r\nFinally in chapter 7, in a preliminary analysis, I begin to dissect
    the genomic island of\r\nspeciation around Rosea/Eluta to understand its evolutionary
    origins. My results show that it\r\nconsists of 5 highly divergent loci, each
    of which is associated with flower colour. Using\r\npatterns of coalescence in
    genealogical trees, I find evidence of staggered selective sweeps\r\nand a persistent
    localized barrier to gene flow within an otherwise permeable genome.\r\nTogether,
    these chapters add to the increasing pool of studies using genealogical\r\napproaches
    to complement and extend site-based statistics to use haplotype structures in\r\nspeciation
    research. By tracking haplotypes directly and connecting genealogical clustering
    to\r\npopulation processes, ARG-based inference promises to provide new insights
    into how local\r\nselective pressures, demographic history, and long-term barriers
    interact to shape the\r\ngenomic architecture of divergence. By underscoring the
    value of ARGs in revealing the finescale origins and maintenance of biodiversity,
    this thesis presents cautious optimism about\r\nthe benefits of using genealogical
    inference to learn more than what site-based statistics\r\ncould tell us."
acknowledged_ssus:
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Arka
  full_name: Pal, Arka
  id: 6AAB2240-CA9A-11E9-9C1A-D9D1E5697425
  last_name: Pal
  orcid: 0000-0002-4530-8469
citation:
  ama: Pal A. Using genealogies to study the genomic basis of species divergence.
    2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20694">10.15479/AT-ISTA-20694</a>
  apa: Pal, A. (2025). <i>Using genealogies to study the genomic basis of species
    divergence</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20694">https://doi.org/10.15479/AT-ISTA-20694</a>
  chicago: Pal, Arka. “Using Genealogies to Study the Genomic Basis of Species Divergence.”
    Institute of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20694">https://doi.org/10.15479/AT-ISTA-20694</a>.
  ieee: A. Pal, “Using genealogies to study the genomic basis of species divergence,”
    Institute of Science and Technology Austria, 2025.
  ista: Pal A. 2025. Using genealogies to study the genomic basis of species divergence.
    Institute of Science and Technology Austria.
  mla: Pal, Arka. <i>Using Genealogies to Study the Genomic Basis of Species Divergence</i>.
    Institute of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20694">10.15479/AT-ISTA-20694</a>.
  short: A. Pal, Using Genealogies to Study the Genomic Basis of Species Divergence,
    Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-11-25T13:19:11Z
date_published: 2025-11-25T00:00:00Z
date_updated: 2026-10-21T08:23:54Z
day: '25'
ddc:
- '576'
- '578'
degree_awarded: PhD
department:
- _id: GradSch
- _id: NiBa
doi: 10.15479/AT-ISTA-20694
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month: '11'
oa: 1
oa_version: Published Version
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project:
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  grant_number: '101055327'
  name: Understanding the evolution of continuous genomes
- _id: 05959E1C-7A3F-11EA-A408-12923DDC885E
  grant_number: P32166
  name: Snapdragon Speciation
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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    status: public
status: public
supervisor:
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
title: Using genealogies to study the genomic basis of species divergence
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  short: CC BY-NC-ND (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
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abstract:
- lang: eng
  text: 'A major goal of speciation research is identifying loci that underpin barriers
    to gene flow. Population genomics takes a ‘bottom-up’ approach, scanning the genome
    for molecular signatures of processes that drive or maintain divergence. However,
    interpreting the ‘genomic landscape’ of speciation is complicated, because genome
    scans conflate multiple processes, most of which are not informative about gene
    flow. However, studying replicated population contrasts, including multiple incidences
    of secondary contact, can strengthen inferences. In this paper, we use linked-read
    sequencing (haplotagging), FST scans and genealogical methods to characterise
    the genomic landscape associated with replicate hybrid zone formation. We studied
    two flower colour varieties of the common snapdragon, Antirrhinum majus subspecies
    majus, that form secondary hybrid zones in multiple independent valleys in the
    Pyrenees. Consistent with past work, we found very low differentiation at one
    well-studied zone (Planoles). However, at a second zone (Avellanet), we found
    stronger differentiation and greater heterogeneity, which we argue is due to differences
    in the amount of introgression following secondary contact. Topology weighting
    of genealogical trees identified loci where haplotype diversity was associated
    with the two snapdragon varieties. Two of the strongest associations were at previously
    identified flower colour loci: Flavia, that affects yellow pigmentation, and Rosea/Eluta,
    two linked loci that affect magenta pigmentation. Preliminary analysis of coalescence
    times provides additional evidence for selective sweeps at these loci and barriers
    to gene flow. Our study highlights the impact of demographic history on the differentiation
    landscape, emphasising the need to distinguish between historical divergence and
    recent introgression.'
acknowledged_ssus:
- _id: ScienComp
acknowledgement: 'We thank ESEB Godfrey Hewitt Mobility Award for supporting AP’s
  research stay at UC Davis. We thank Tom Ellis, Parvathy Surendranadh, and other
  Barton Group and Coop Lab members for stimulating discussions. We are grateful to
  all the interns and volunteers who have helped us with fieldwork. We thank Eva Salmerón
  Mateu for her assistance in fieldwork logistics at the field station, El Serrat.
  We are grateful to Enrico Coen and his research group for providing the Antirrhinum
  molle PoolSeq data used in the allele polarisation. We are also thankful to Enrico
  Coen and Cristophe Thébaud for discovering the Avellanet hybrid zone, followed up
  with sampling led by D.L.F. in 2017. The study was supported by Austrian Science
  Fund (FWF) Grant (Snapdragon Speciation P32166, awarded to D.L.F.); ERC (Advanced
  Grant HaplotypeStructure 101055327, awarded to NHB); ERC (POC Grant 101069216, awarded
  to Y.F.C.) and the National Institutes of Health (NIH R35 GM136290, awarded to G.C.).
  Y.F.C. was supported by the Max Planck Society. Computing infrastructure for bioinformatics
  and analyses was provided by ISTA High Performance Cluster. '
article_number: e70067
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Arka
  full_name: Pal, Arka
  id: 6AAB2240-CA9A-11E9-9C1A-D9D1E5697425
  last_name: Pal
  orcid: 0000-0002-4530-8469
- first_name: Daria
  full_name: Shipilina, Daria
  id: 428A94B0-F248-11E8-B48F-1D18A9856A87
  last_name: Shipilina
  orcid: 0000-0002-1145-9226
- first_name: Alan
  full_name: Le Moan, Alan
  last_name: Le Moan
- first_name: Adrian J.
  full_name: Mcnairn, Adrian J.
  last_name: Mcnairn
- first_name: Jennifer K.
  full_name: Grenier, Jennifer K.
  last_name: Grenier
- first_name: Marek
  full_name: Kucka, Marek
  last_name: Kucka
- first_name: Graham
  full_name: Coop, Graham
  last_name: Coop
- first_name: Yingguang Frank
  full_name: Chan, Yingguang Frank
  last_name: Chan
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
- first_name: David
  full_name: Field, David
  id: 419049E2-F248-11E8-B48F-1D18A9856A87
  last_name: Field
  orcid: 0000-0002-4014-8478
- first_name: Sean
  full_name: Stankowski, Sean
  id: 43161670-5719-11EA-8025-FABC3DDC885E
  last_name: Stankowski
citation:
  ama: Pal A, Shipilina D, Le Moan A, et al. Genealogical analysis of replicate flower
    colour hybrid zones in Antirrhinum. <i>Molecular Ecology</i>. 2025;34(22). doi:<a
    href="https://doi.org/10.1111/mec.70067">10.1111/mec.70067</a>
  apa: Pal, A., Shipilina, D., Le Moan, A., Mcnairn, A. J., Grenier, J. K., Kucka,
    M., … Stankowski, S. (2025). Genealogical analysis of replicate flower colour
    hybrid zones in Antirrhinum. <i>Molecular Ecology</i>. Wiley. <a href="https://doi.org/10.1111/mec.70067">https://doi.org/10.1111/mec.70067</a>
  chicago: Pal, Arka, Daria Shipilina, Alan Le Moan, Adrian J. Mcnairn, Jennifer K.
    Grenier, Marek Kucka, Graham Coop, et al. “Genealogical Analysis of Replicate
    Flower Colour Hybrid Zones in Antirrhinum.” <i>Molecular Ecology</i>. Wiley, 2025.
    <a href="https://doi.org/10.1111/mec.70067">https://doi.org/10.1111/mec.70067</a>.
  ieee: A. Pal <i>et al.</i>, “Genealogical analysis of replicate flower colour hybrid
    zones in Antirrhinum,” <i>Molecular Ecology</i>, vol. 34, no. 22. Wiley, 2025.
  ista: Pal A, Shipilina D, Le Moan A, Mcnairn AJ, Grenier JK, Kucka M, Coop G, Chan
    YF, Barton NH, Field D, Stankowski S. 2025. Genealogical analysis of replicate
    flower colour hybrid zones in Antirrhinum. Molecular Ecology. 34(22), e70067.
  mla: Pal, Arka, et al. “Genealogical Analysis of Replicate Flower Colour Hybrid
    Zones in Antirrhinum.” <i>Molecular Ecology</i>, vol. 34, no. 22, e70067, Wiley,
    2025, doi:<a href="https://doi.org/10.1111/mec.70067">10.1111/mec.70067</a>.
  short: A. Pal, D. Shipilina, A. Le Moan, A.J. Mcnairn, J.K. Grenier, M. Kucka, G.
    Coop, Y.F. Chan, N.H. Barton, D. Field, S. Stankowski, Molecular Ecology 34 (2025).
corr_author: '1'
date_created: 2025-08-17T22:01:37Z
date_published: 2025-11-01T00:00:00Z
date_updated: 2026-11-04T23:31:18Z
day: '01'
ddc:
- '570'
department:
- _id: NiBa
doi: 10.1111/mec.70067
external_id:
  isi:
  - '001546622100001'
file:
- access_level: open_access
  checksum: c586fc674df4e7dd6e43aef87a52c6f6
  content_type: application/pdf
  creator: dernst
  date_created: 2026-01-05T13:47:47Z
  date_updated: 2026-01-05T13:47:47Z
  file_id: '20958'
  file_name: 2025_MolecEcology_Pal.pdf
  file_size: 9886694
  relation: main_file
  success: 1
file_date_updated: 2026-01-05T13:47:47Z
fulldoi: https://doi.org/10.1111/mec.70067
has_accepted_license: '1'
intvolume: '        34'
isi: 1
issue: '22'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 05959E1C-7A3F-11EA-A408-12923DDC885E
  grant_number: P32166
  name: Snapdragon Speciation
- _id: bd6958e0-d553-11ed-ba76-86eba6a76c00
  grant_number: '101055327'
  name: Understanding the evolution of continuous genomes
publication: Molecular Ecology
publication_identifier:
  eissn:
  - 1365-294X
  issn:
  - 0962-1083
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/snapdragon-secrets/
  record:
  - id: '20694'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Genealogical analysis of replicate flower colour hybrid zones in Antirrhinum
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 34
year: '2025'
...
---
OA_place: publisher
_id: '19271'
abstract:
- lang: eng
  text: "The medial habenula (MHb) is implicated in regulating emotional responses\r\nto
    aversive events. Studies in zebrafish have identified a remarkable morphological\r\nleft-right
    asymmetry in the dorsal habenula (zebrafish equivalent of mammalian\r\nMHb)-to-interpeduncular
    nucleus (IPN) pathway and its left-side specific role in\r\nmodulating fear responses.
    However, there is little evidence for structural or\r\nfunctional lateralization
    in the mammalian MHb-IPN pathway.\r\nHere, I investigated the synaptic properties
    of the left and right MHb\r\nafferents to the IPN in mice and addressed whether
    these synaptic connections\r\nselectively influence the expression of conditioned
    fear in mice. My findings reveal\r\nthat each individual IPN neuron receives inputs
    from both left and right MHb.\r\nElectrophysiological recordings from the same
    postsynaptic IPN neurons\r\ndemonstrate that the left MHb-originating synapses
    exhibit lower release\r\nprobability and higher \U0001D6FE-aminobutyric acid type
    B receptor (GABABR)-mediated\r\npotentiation compared to the right MHb-originating
    synapses. Interestingly,\r\nchemogenetic inhibition of cholinergic neurons in
    the left but not the right MHb\r\nsignificantly attenuated cue-dependent fear
    recall. Furthermore, conditional\r\ndeletion of GABABR in the left MHb interfered
    with the recall of cued fear memory,\r\nwhereas that in the right MHb neurons
    spared fear memory expression.\r\nCollectively, I demonstrate a functional asymmetry
    of the MHb in mice,\r\nrevealing a predominant role for GABABR-mediated signaling
    in the left MHb-IPN\r\npathway in the modulation of fear memories. These findings
    suggest that\r\nlateralized pathways could represent a fundamental principle in
    the neural\r\nregulation of emotion across species."
acknowledged_ssus:
- _id: PreCl
- _id: M-Shop
acknowledgement: "I would like to thank the European Research Council and European
  Commission, under the European Union’s Horizon 2020 research and innovation program
  (ERC grant agreement no. 694539 to Ryuichi Shigemoto and the Marie Skłodowska-Curie
  grant agreement no. 665385 to Cihan Önal), and the Austrian Neuroscience Association
  for providing financial support and opportunities, which were important in allowing
  me to present my work. I also wish to thank the\r\nPreclinical Facility, especially
  Michael Schunn, for always welcoming me from my earliest days as an intern. My gratitude
  goes as well to the Miba Machine Shop, in particular Todor Asenov, Astrit Arslani,
  and Thomas Menner, whose technical expertise often saved the day."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
citation:
  ama: Önal C. Asymmetrical modulation of fear expression via GABAB receptors in the
    mouse medial habenula. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19271">10.15479/AT-ISTA-19271</a>
  apa: Önal, C. (2025). <i>Asymmetrical modulation of fear expression via GABAB receptors
    in the mouse medial habenula</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT-ISTA-19271">https://doi.org/10.15479/AT-ISTA-19271</a>
  chicago: Önal, Cihan. “Asymmetrical Modulation of Fear Expression via GABAB Receptors
    in the Mouse Medial Habenula.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-19271">https://doi.org/10.15479/AT-ISTA-19271</a>.
  ieee: C. Önal, “Asymmetrical modulation of fear expression via GABAB receptors in
    the mouse medial habenula,” Institute of Science and Technology Austria, 2025.
  ista: Önal C. 2025. Asymmetrical modulation of fear expression via GABAB receptors
    in the mouse medial habenula. Institute of Science and Technology Austria.
  mla: Önal, Cihan. <i>Asymmetrical Modulation of Fear Expression via GABAB Receptors
    in the Mouse Medial Habenula</i>. Institute of Science and Technology Austria,
    2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-19271">10.15479/AT-ISTA-19271</a>.
  short: C. Önal, Asymmetrical Modulation of Fear Expression via GABAB Receptors in
    the Mouse Medial Habenula, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-02-28T14:15:53Z
date_published: 2025-03-04T00:00:00Z
date_updated: 2026-10-21T08:33:44Z
day: '04'
ddc:
- '570'
- '571'
- '573'
- '599'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/AT-ISTA-19271
ec_funded: 1
file:
- access_level: closed
  checksum: c1a4d75a7471de9f954697b06cd18d28
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: hoenal
  date_created: 2025-02-28T13:57:01Z
  date_updated: 2026-02-01T23:30:02Z
  embargo_to: open_access
  file_id: '19272'
  file_name: Cihan_Onal_Thesis_Final.docx
  file_size: 25869143
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  checksum: de4e62147ab9f04098dc8cd898c630da
  content_type: application/pdf
  creator: hoenal
  date_created: 2025-02-28T13:57:04Z
  date_updated: 2026-02-01T23:30:02Z
  embargo: 2026-02-01
  file_id: '19273'
  file_name: Cihan_Onal_Thesis_Final_pdfa.pdf
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  relation: main_file
file_date_updated: 2026-02-01T23:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-19271
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication_identifier:
  eissn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '9437'
    relation: part_of_dissertation
    status: public
  - id: '15084'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse
  medial habenula
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: publisher
_id: '19478'
abstract:
- lang: eng
  text: "Auxin is one of the most important phytohormones, playing a crucial role
    in plant growth and \r\ndevelopment. Genetic studies in Arabidopsis have identified
    core components of auxin \r\nsignalling and established the classical transcriptional
    regulation mechanism. This classical \r\nparadigm recognizes TRANSPORT INHIBITOR
    RESPONSE 1 (TIR1)/AUXIN \r\nSIGNALLING F-BOX (AFB) proteins as auxin receptors
    possessing E3 ubiquitin ligase \r\nactivity. Auxin functions as a \"molecular
    glue\" enhancing TIR1/AFB-Aux/IAA \r\n(AUXIN/INDOLE-3-ACETIC ACID) inhibitor interactions,
    leading to Aux/IAAs’ \r\nubiquitination and degradation. This process releases
    AUXIN RESPONSE FACTORs (ARFs) \r\nfrom repression, enabling transcriptional activation
    of auxin-responsive genes. Notably, the \r\ndiscovery of adenylate cyclase (AC)
    activity in TIR1/AFBs, catalysing cAMP production from \r\nATP, presents novel
    transcriptional regulatory possibilities, though cAMP's mechanistic role \r\nin
    auxin signalling remains unclear. Beyond transcriptional regulation (slow response)
    a non\r\ntranscriptional pathway (rapid response) mediated by AFB1 also exists,
    as auxin triggers rapid \r\nroot growth inhibition within 30 seconds. How TIR1
    and AFB1, with their distinct subcellular \r\nlocalizations, differentially regulate
    transcriptional and non-transcriptional processes remains \r\nunclear. To address
    these two key questions, this study conducted the following investigations.  \r\nTIR1
    and AFB1 display distinct subcellular localization patterns, with AFB1 specifically
    \r\nmediating auxin-induced rapid root growth inhibition. To examine whether subcellular
    \r\nlocalization differences contribute to functional divergence between TIR1
    and AFB1, we \r\nutilized microfluidic systems combined with genetic complementation
    assays. Nuclear export \r\nsignal-fused TIR1 failed to rescue the rapid response
    defects observed in afb1 mutants. In \r\ncontrast, nuclear localization signal-fused
    AFB1 exhibited dual functional deficiencies: it \r\nneither restored the rapid
    response impairment in afb1 mutants nor compensated for \r\ntranscriptional regulation
    defects in tir1 mutants which limitation stemmed from AFB1's \r\nintrinsic incapacity
    to assemble functional SCF complexes. These results collectively establish \r\nthat
    the functional specialization of TIR1 and AFB1 is governed by both their subcellular
    \r\ncompartmentalization and inherent biochemical characteristics. \r\nThe mechanism
    by which cAMP derived from the auxin receptor TIR1/AFB modulates \r\ntranscriptional
    regulation remains undefined. To address this, we genetically dissociated TIR1
    \r\nAC activity from its E3 ubiquitin ligase function to investigate cAMP's signalling
    role. AC\r\ninactivating mutations preserved TIR1-mediated Aux/IAAs’ degradation
    but abolished ARF\r\ni \r\ndependent transcriptional activation. tir1afb2 mutants
    expressing AC-deficient TIR1 variants \r\nfailed to restore transcriptional responses.
    Crucially, compartmentalized cAMP accumulation \r\nwithin Aux/IAA - ARF complexes
    vicinity triggered auxin signalling independently of both \r\nauxin perception
    and Aux/IAAs’ degradation, confirming its secondary messenger identity. \r\nFurther
    mechanistic analysis demonstrated cAMP directly interact with ARF. cAMP \r\ndirectly
    promotes ARF dissociation from Aux/IAA repressors and enhances ARF \r\nhomodimerization.
    Genetic complementation assays revealed that ARF mutants lacking \r\nconserved
    cAMP-binding motifs exhibited partial functional recovery, providing direct \r\nevidence
    for cAMP-ARF physical interaction during signal propagation. \r\nThese findings
    collectively challenge the established model of auxin signalling and define \r\na
    novel TIR1-cAMP-ARF regulatory axis, substantially advancing our comprehension
    of \r\nauxin-mediated physiological regulation. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "This project was funded by the European Research Council Advanced
  Grant (ETAP-742985),\r\nEuropean Research Council (ERC; 101142681 CYNIPS), Austrian
  Science Fund (FWF; P\r\n37051-B)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Huihuang
  full_name: Chen, Huihuang
  id: 83c96512-15b2-11ec-abd3-b7eede36184f
  last_name: Chen
citation:
  ama: Chen H. The cAMP second messenger in auxin signalling. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19478">10.15479/AT-ISTA-19478</a>
  apa: Chen, H. (2025). <i>The cAMP second messenger in auxin signalling</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-19478">https://doi.org/10.15479/AT-ISTA-19478</a>
  chicago: Chen, Huihuang. “The CAMP Second Messenger in Auxin Signalling.” Institute
    of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-19478">https://doi.org/10.15479/AT-ISTA-19478</a>.
  ieee: H. Chen, “The cAMP second messenger in auxin signalling,” Institute of Science
    and Technology Austria, 2025.
  ista: Chen H. 2025. The cAMP second messenger in auxin signalling. Institute of
    Science and Technology Austria.
  mla: Chen, Huihuang. <i>The CAMP Second Messenger in Auxin Signalling</i>. Institute
    of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-19478">10.15479/AT-ISTA-19478</a>.
  short: H. Chen, The CAMP Second Messenger in Auxin Signalling, Institute of Science
    and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-04-04T07:48:24Z
date_published: 2025-04-04T00:00:00Z
date_updated: 2026-10-23T07:25:54Z
day: '04'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JiFr
doi: 10.15479/AT-ISTA-19478
doi_confirm: '1'
ec_funded: 1
file:
- access_level: closed
  checksum: b154973663a1bba505683faab7ae5ead
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: hchen
  date_created: 2025-04-08T08:00:07Z
  date_updated: 2026-10-08T22:30:02Z
  embargo_to: open_access
  file_id: '19526'
  file_name: Thesis_0403_Huihuang.docx
  file_size: 16344814
  relation: source_file
- access_level: open_access
  checksum: 0099565f024388830c125ec17375c1a0
  content_type: application/pdf
  creator: hchen
  date_created: 2025-04-08T08:00:06Z
  date_updated: 2026-10-09T22:30:03Z
  embargo: 2026-10-08
  file_id: '19527'
  file_name: Thesis_0406_PDFA_Huihuang_1.pdf
  file_size: 8482147
  relation: main_file
file_date_updated: 2026-10-09T22:30:03Z
fulldoi: https://doi.org/10.15479/AT-ISTA-19478
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '118'
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 7bcece63-9f16-11ee-852c-ae94e099eeb6
  grant_number: P37051
  name: Guanylate cyclase activity of TIR1/AFBs auxin receptors
- _id: 8f347782-16d5-11f0-9cad-8c19706ee739
  grant_number: '101142681'
  name: Cyclic nucleotides as second messengers in plants
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '19421'
    relation: part_of_dissertation
    status: public
  - id: '13212'
    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: The cAMP second messenger in auxin signalling
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
OA_place: publisher
_id: '20467'
abstract:
- lang: eng
  text: "Prostaglandins play a central role in the inflammatory response. Prostaglandins
    are synthesized \r\nin a rate-limiting manner by the enzyme cyclooxygenase (Cox),
    which exists in two isoforms: \r\nthe Cox-2 and Cox-1 isoforms. Traditionally,
    Cox-1 is thought to mediate homeostatic \r\nfunctions due to its constitutive
    expression due to its constitutive expression, whereas Cox-2 is \r\ntemporary
    induced in response to inflammatory stimuli and is associated with the inflammatory
    \r\nresponse. Interestingly, in the central nervous system, Cox-1 is predominantly
    expressed in \r\nmicroglia. As the resident immune cells of the brain, microglia
    play a key role in inflammation. \r\nCox-1 expressing microglia are increased
    in neurodegenerative diseases, and both global \r\nknockout of Cox-1 and selective
    Cox-1 inhibition has been shown to ameliorate inflammatory \r\neffects in neurodegenerative
    diseases. However, direct evidence elucidating how microglial \r\nCox-1 expression
    influences their response to insults remains limited and warrants further \r\ninvestigation.
    \r\nFirst, I utilize the optic nerve crush (ONC) model to study the microglial
    response to injury and \r\ninflammation, confirming a reactive microglial response
    in both the crushed and uninjured \r\ncontralateral retina using CD68 expression
    and morphological analysis. While previous studies \r\nreported retinal ganglion
    cell (RGC) loss in the contralateral eye, I did not observe this, \r\nsuggesting
    that unilateral ONC induces microglial activation in the contralateral eye without
    \r\nRGC degeneration. To explore the role of Cox-1 in this response, I generated
    a mouse model \r\nwith microglia-specific deletion of Cox-1. After ONC, these
    mice exhibited an attenuated \r\nmicroglial response in both the ipsilateral and
    contralateral retinas, as well as in visual \r\nprocessing areas of the brain.
    Notably, Cox-2 does not show any expression after ONC in both \r\nwild-type and
    Cox-1 knockout mice Additionally, Cox-1KO mice show a reduction in \r\nphagocytic
    cups and a reduction in microglia proliferation after ONC. However, due to \r\nreproducibility
    problems of the observed phenotype, even after the generation of two new \r\nmouse
    models, I cannot draw any definitive conclusions based on the data. \r\nNext,
    due to the ambiguity of the mouse model, I explored an alternative route to investigate
    \r\nfunctional consequences of Cox-1 in microglia. I generated a COX1 knock-out
    human induced \r\npluripotent cell (hIPSC) line using CRISPR/Cas9. These cells
    are were differentiated in \r\nmicroglia-like cells and integrated in dissociated
    retinal organoids according to protocols \r\ndeveloped in our lab. In response
    to LPS and POLY(I:C) stimulation, the release and expression \r\nof cytokines
    and chemokines was decreased in COX1 knockout cells. However, the \r\nprostaglandin
    PGE2 was not increased in microglia-like cells in both control and COX1 \r\nknockout
    cells.  \r\nOverall, the results from the COX1 knock-out microglia-like cells
    suggests that COX1 \r\nexpression in microglia play a role in neuroinflammation
    by affecting the release of \r\ninflammatory cytokines and chemokines. Hereby
    further challenging that the dogma of the \r\nCox-1 isoform involved in housekeeping
    functions and the Cox-2 isoform involved in \r\ninflammation applies for the central
    nervous system.   "
acknowledged_ssus:
- _id: Bio
- _id: SSU
- _id: PreCl
- _id: LifeSc
acknowledgement: "The work presented in this Thesis was carried out at the Institute
  of Science and Technology\r\nAustria (ISTA), and was supported by the Austrian Science
  Fund (FWF) [10.55776/P37131].\r\nI would like to thank the Scientific Service Units
  (SSU) of ISTA for the provided resources,\r\nspecifically the Imaging and Optics
  Facility (IOF), the Lab Support Facility (LSF), and the\r\nPre-Clinical Facility
  (PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael\r\nSchunn, for
  mouse colony management and support. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Florianne E
  full_name: Miteva, Florianne E
  id: 3526230C-F248-11E8-B48F-1D18A9856A87
  last_name: Miteva
citation:
  ama: Miteva FE. The role of cyclooxygenase 1 on microglial response to inflammatory
    stressors. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20467">10.15479/AT-ISTA-20467</a>
  apa: Miteva, F. E. (2025). <i>The role of cyclooxygenase 1 on microglial response
    to inflammatory stressors</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT-ISTA-20467">https://doi.org/10.15479/AT-ISTA-20467</a>
  chicago: Miteva, Florianne E. “The Role of Cyclooxygenase 1 on Microglial Response
    to Inflammatory Stressors.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-20467">https://doi.org/10.15479/AT-ISTA-20467</a>.
  ieee: F. E. Miteva, “The role of cyclooxygenase 1 on microglial response to inflammatory
    stressors,” Institute of Science and Technology Austria, 2025.
  ista: Miteva FE. 2025. The role of cyclooxygenase 1 on microglial response to inflammatory
    stressors. Institute of Science and Technology Austria.
  mla: Miteva, Florianne E. <i>The Role of Cyclooxygenase 1 on Microglial Response
    to Inflammatory Stressors</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-20467">10.15479/AT-ISTA-20467</a>.
  short: F.E. Miteva, The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory
    Stressors, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-10-14T10:24:41Z
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title: The role of cyclooxygenase 1 on microglial response to inflammatory stressors
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