---
_id: '15016'
abstract:
- lang: eng
  text: 'The development, evolution, and function of the vertebrate central nervous
    system (CNS) can be best studied using diverse model organisms. Amphibians, with
    their unique phylogenetic position at the transition between aquatic and terrestrial
    lifestyles, are valuable for understanding the origin and evolution of the tetrapod
    brain and spinal cord. Their metamorphic developmental transitions and unique
    regenerative abilities also facilitate the discovery of mechanisms for neural
    circuit remodeling and replacement. The genetic toolkit for amphibians, however,
    remains limited, with only a few species having sequenced genomes and a small
    number of transgenic lines available. In mammals, recombinant adeno-associated
    viral vectors (AAVs) have become a powerful alternative to genome modification
    for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable
    neuronal transduction in both developing and adult animals with low toxicity and
    spatial, temporal, and cell-type specificity. However, AAVs have never been shown
    to transduce amphibian cells efficiently. To bridge this gap, we established a
    simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related
    amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the
    salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic
    animals. For each species, we successfully identified at least two AAV serotypes
    capable of infecting the CNS; however, no pan-amphibian serotype was identified,
    indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based
    strategy that targets isochronic cohorts of developing neurons – a critical tool
    for parsing neural circuit assembly. Finally, to enable visualization and manipulation
    of neural circuits, we identified AAV variants for retrograde tracing of neuronal
    projections in adult animals. Our findings expand the toolkit for amphibians to
    include AAVs, establish a generalizable workflow for AAV screening in non-canonical
    research organisms, generate testable hypotheses for the evolution of AAV tropism,
    and lay the foundation for modern cross-species comparisons of vertebrate CNS
    development, function, and evolution. '
acknowledgement: "We would like to extend our thanks to members of the Sweeney, Tosches,
  Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this
  project, discussion and support.\r\nWe additionally thank the Beckman Institute
  Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools),
  Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto
  Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as
  Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo
  do these experiments, we have also benefited from the tremendous support of our
  animal care and imaging facilities at our respective institutions, as well as the
  amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource
  Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation
  (NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United
  States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.);
  NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation
  Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551
  (L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award
  number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term
  Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship
  DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H)."
article_processing_charge: No
author:
- first_name: Eliza C.B.
  full_name: Jaeger, Eliza C.B.
  last_name: Jaeger
- first_name: David
  full_name: Vijatovic, David
  id: cf391e77-ec3c-11ea-a124-d69323410b58
  last_name: Vijatovic
- first_name: Astrid
  full_name: Deryckere, Astrid
  last_name: Deryckere
- first_name: Nikol
  full_name: Zorin, Nikol
  last_name: Zorin
- first_name: Akemi L.
  full_name: Nguyen, Akemi L.
  last_name: Nguyen
- first_name: Georgiy
  full_name: Ivanian, Georgiy
  id: eaf2b366-cfd1-11ee-bbdf-c8790f800a05
  last_name: Ivanian
- first_name: Jamie
  full_name: Woych, Jamie
  last_name: Woych
- first_name: Rebecca C
  full_name: Arnold, Rebecca C
  id: d6cce458-14c9-11ed-a755-c1c8fc6fde6f
  last_name: Arnold
- first_name: Alonso
  full_name: Ortega Gurrola, Alonso
  last_name: Ortega Gurrola
- first_name: Arik
  full_name: Shvartsman, Arik
  last_name: Shvartsman
- first_name: Francesca
  full_name: Barbieri, Francesca
  id: a9492887-8972-11ed-ae7b-bfae10998254
  last_name: Barbieri
- first_name: Florina-Alexandra
  full_name: Toma, Florina-Alexandra
  id: 85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5
  last_name: Toma
- first_name: Gary J.
  full_name: Gorbsky, Gary J.
  last_name: Gorbsky
- first_name: Marko E.
  full_name: Horb, Marko E.
  last_name: Horb
- first_name: Hollis T.
  full_name: Cline, Hollis T.
  last_name: Cline
- first_name: Timothy F.
  full_name: Shay, Timothy F.
  last_name: Shay
- first_name: Darcy B.
  full_name: Kelley, Darcy B.
  last_name: Kelley
- first_name: Ayako
  full_name: Yamaguchi, Ayako
  last_name: Yamaguchi
- first_name: Mark
  full_name: Shein-Idelson, Mark
  last_name: Shein-Idelson
- first_name: Maria Antonietta
  full_name: Tosches, Maria Antonietta
  last_name: Tosches
- first_name: Lora Beatrice Jaeger
  full_name: Sweeney, Lora Beatrice Jaeger
  id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
  last_name: Sweeney
  orcid: 0000-0001-9242-5601
citation:
  ama: Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to
    trace neural development and connectivity across amphibians. <i>bioRxiv</i>. doi:<a
    href="https://doi.org/10.1101/2024.02.15.580289">10.1101/2024.02.15.580289</a>
  apa: Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian,
    G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development
    and connectivity across amphibians. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.02.15.580289">https://doi.org/10.1101/2024.02.15.580289</a>
  chicago: Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi
    L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools
    to Trace Neural Development and Connectivity across Amphibians.” <i>BioRxiv</i>,
    n.d. <a href="https://doi.org/10.1101/2024.02.15.580289">https://doi.org/10.1101/2024.02.15.580289</a>.
  ieee: E. C. B. Jaeger <i>et al.</i>, “Adeno-associated viral tools to trace neural
    development and connectivity across amphibians,” <i>bioRxiv</i>. .
  ista: Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych
    J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ,
    Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA,
    Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity
    across amphibians. bioRxiv, <a href="https://doi.org/10.1101/2024.02.15.580289">10.1101/2024.02.15.580289</a>.
  mla: Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development
    and Connectivity across Amphibians.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.02.15.580289">10.1101/2024.02.15.580289</a>.
  short: E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian,
    J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma,
    G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M.
    Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).
date_created: 2024-02-20T09:20:32Z
date_published: 2024-02-16T00:00:00Z
date_updated: 2024-02-20T09:34:25Z
day: '16'
department:
- _id: LoSw
- _id: MaDe
- _id: GaNo
doi: 10.1101/2024.02.15.580289
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.02.15.580289
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
  grant_number: FTI21-D-046
  name: Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während
    der Metamorphose von Xenopus
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
  grant_number: '101041551'
  name: Development and Evolution of Tetrapod Motor Circuits
publication: bioRxiv
publication_status: submitted
status: public
title: Adeno-associated viral tools to trace neural development and connectivity across
  amphibians
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '13097'
abstract:
- lang: eng
  text: 'Vertebrate movement is orchestrated by spinal inter- and motor neurons that,
    together with sensory and cognitive input, produce dynamic motor behaviors. These
    behaviors vary from the simple undulatory swimming of fish and larval aquatic
    species to the highly coordinated running, reaching and grasping of mice, humans
    and other mammals. This variation raises the fundamental question of how spinal
    circuits have changed in register with motor behavior. In simple, undulatory fish,
    exemplified by the lamprey, two broad classes of interneurons shape motor neuron
    output: ipsilateral-projecting excitatory neurons, and commissural-projecting
    inhibitory neurons. An additional class of ipsilateral inhibitory neurons is required
    to generate escape swim behavior in larval zebrafish and tadpoles. In limbed vertebrates,
    a more complex spinal neuron composition is observed. In this review, we provide
    evidence that movement elaboration correlates with an increase and specialization
    of these three basic interneuron types into molecularly, anatomically, and functionally
    distinct subpopulations. We summarize recent work linking neuron types to movement-pattern
    generation across fish, amphibians, reptiles, birds and mammals.'
acknowledgement: 'This work was supported by the ERC Starting grant, ERC-2021-STG
  #101041551.'
article_number: '1146449'
article_processing_charge: Yes
article_type: original
author:
- first_name: Alexia C
  full_name: Wilson, Alexia C
  id: 5230e794-15b2-11ec-abd3-e2d5335ebd1d
  last_name: Wilson
- first_name: Lora Beatrice Jaeger
  full_name: Sweeney, Lora Beatrice Jaeger
  id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
  last_name: Sweeney
  orcid: 0000-0001-9242-5601
citation:
  ama: 'Wilson AC, Sweeney LB. Spinal cords: Symphonies of interneurons across species.
    <i>Frontiers in Neural Circuits</i>. 2023;17. doi:<a href="https://doi.org/10.3389/fncir.2023.1146449">10.3389/fncir.2023.1146449</a>'
  apa: 'Wilson, A. C., &#38; Sweeney, L. B. (2023). Spinal cords: Symphonies of interneurons
    across species. <i>Frontiers in Neural Circuits</i>. Frontiers. <a href="https://doi.org/10.3389/fncir.2023.1146449">https://doi.org/10.3389/fncir.2023.1146449</a>'
  chicago: 'Wilson, Alexia C, and Lora B. Sweeney. “Spinal Cords: Symphonies of Interneurons
    across Species.” <i>Frontiers in Neural Circuits</i>. Frontiers, 2023. <a href="https://doi.org/10.3389/fncir.2023.1146449">https://doi.org/10.3389/fncir.2023.1146449</a>.'
  ieee: 'A. C. Wilson and L. B. Sweeney, “Spinal cords: Symphonies of interneurons
    across species,” <i>Frontiers in Neural Circuits</i>, vol. 17. Frontiers, 2023.'
  ista: 'Wilson AC, Sweeney LB. 2023. Spinal cords: Symphonies of interneurons across
    species. Frontiers in Neural Circuits. 17, 1146449.'
  mla: 'Wilson, Alexia C., and Lora B. Sweeney. “Spinal Cords: Symphonies of Interneurons
    across Species.” <i>Frontiers in Neural Circuits</i>, vol. 17, 1146449, Frontiers,
    2023, doi:<a href="https://doi.org/10.3389/fncir.2023.1146449">10.3389/fncir.2023.1146449</a>.'
  short: A.C. Wilson, L.B. Sweeney, Frontiers in Neural Circuits 17 (2023).
date_created: 2023-05-28T22:01:04Z
date_published: 2023-04-26T00:00:00Z
date_updated: 2024-01-31T10:15:53Z
day: '26'
ddc:
- '570'
department:
- _id: LoSw
doi: 10.3389/fncir.2023.1146449
external_id:
  isi:
  - '000984606200001'
  pmid:
  - '37180760'
file:
- access_level: open_access
  checksum: 7efd06de284a28e91e97127611a9c3fd
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-03T13:33:21Z
  date_updated: 2024-01-03T13:33:21Z
  file_id: '14729'
  file_name: 2023_FrontiersNeuralCircuits_Wilson.pdf
  file_size: 6667157
  relation: main_file
  success: 1
file_date_updated: 2024-01-03T13:33:21Z
has_accepted_license: '1'
intvolume: '        17'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
  grant_number: '101041551'
  name: Development and Evolution of Tetrapod Motor Circuits
publication: Frontiers in Neural Circuits
publication_identifier:
  issn:
  - 1662-5110
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Spinal cords: Symphonies of interneurons across species'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2023'
...
---
_id: '10918'
abstract:
- lang: eng
  text: Cellular metabolism must adapt to changing demands to enable homeostasis.
    During immune responses or cancer metastasis, cells leading migration into challenging
    environments require an energy boost, but what controls this capacity is unclear.
    Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by
    CG9005), which supports macrophage invasion into the germband of Drosophila by
    controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of
    Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate
    reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial
    bioenergetics. Then Porthos supports ribosome assembly and thereby raises the
    translational efficiency of a subset of mRNAs, including those affecting mitochondrial
    functions, the electron transport chain, and metabolism. Mitochondrial respiration
    measurements, metabolomics, and live imaging indicate that Atossa and Porthos
    power up OxPhos and energy production to promote the forging of a path into tissues
    by leading macrophages. Since many crucial physiological responses require increases
    in mitochondrial energy output, this previously undescribed genetic program may
    modulate a wide range of cellular behaviors.
acknowledged_ssus:
- _id: Bio
acknowledgement: "We thank the DGRC (NIH grant 2P40OD010949-10A1) for plasmids, the
  BDSC (NIH grant P40OD018537) and the VDRC for fly stocks, FlyBase for essential
  genomic information, the BDGP in situ database for data (Tomancak et al, 2007),
  the IST Austria Bioimaging facility for support, the VBC Core Facilities for RNA
  sequencing and analysis, and C. Guet, C. Navarro, C. Desplan, T. Lecuit, I. Miguel-Aliaga,
  and Siekhaus group members for comments on the manuscript. The VBCF Metabolomics
  Facility is funded by the City of Vienna through the Vienna Business Agency. This
  work was supported by the Marie Curie CIG 334077/IRTIM (DES), Austrian Science Fund
  (FWF) Lise Meitner Fellowship M2379-B28 (MA and DES), Austrian Science Fund (FWF)
  grant ASI_FWF01_P29638S (DES), NIH/NIGMS (R01GM111779-06 (PR), RO1GM135628-01 (PR),
  European Research Council (ERC) grant no. 677006 “CMIL” (AB), and Natural Sciences
  and Engineering Research Council of Canada\r\n(RGPIN-2019-06766) (TRH). "
article_number: e109049
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Shamsi
  full_name: Emtenani, Shamsi
  id: 49D32318-F248-11E8-B48F-1D18A9856A87
  last_name: Emtenani
  orcid: 0000-0001-6981-6938
- first_name: Elliot T
  full_name: Martin, Elliot T
  last_name: Martin
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Jakob-Wendelin
  full_name: Genger, Jakob-Wendelin
  last_name: Genger
- first_name: Thomas
  full_name: Köcher, Thomas
  last_name: Köcher
- first_name: Maria
  full_name: Akhmanova, Maria
  id: 3425EC26-F248-11E8-B48F-1D18A9856A87
  last_name: Akhmanova
  orcid: 0000-0003-1522-3162
- first_name: Mariana
  full_name: Pereira Guarda, Mariana
  id: 6de81d9d-e2f2-11eb-945a-af8bc2a60b26
  last_name: Pereira Guarda
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Andreas
  full_name: Bergthaler, Andreas
  last_name: Bergthaler
- first_name: Thomas R
  full_name: Hurd, Thomas R
  last_name: Hurd
- first_name: Prashanth
  full_name: Rangan, Prashanth
  last_name: Rangan
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: Emtenani S, Martin ET, György A, et al. Macrophage mitochondrial bioenergetics
    and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The
    Embo Journal</i>. 2022;41. doi:<a href="https://doi.org/10.15252/embj.2021109049">10.15252/embj.2021109049</a>
  apa: Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Köcher,
    T., … Siekhaus, D. E. (2022). Macrophage mitochondrial bioenergetics and tissue
    invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The Embo Journal</i>.
    Embo Press. <a href="https://doi.org/10.15252/embj.2021109049">https://doi.org/10.15252/embj.2021109049</a>
  chicago: Emtenani, Shamsi, Elliot T Martin, Attila György, Julia Bicher, Jakob-Wendelin
    Genger, Thomas Köcher, Maria Akhmanova, et al. “Macrophage Mitochondrial Bioenergetics
    and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The
    Embo Journal</i>. Embo Press, 2022. <a href="https://doi.org/10.15252/embj.2021109049">https://doi.org/10.15252/embj.2021109049</a>.
  ieee: S. Emtenani <i>et al.</i>, “Macrophage mitochondrial bioenergetics and tissue
    invasion are boosted by an Atossa-Porthos axis in Drosophila,” <i>The Embo Journal</i>,
    vol. 41. Embo Press, 2022.
  ista: Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova
    M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022.
    Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos
    axis in Drosophila. The Embo Journal. 41, e109049.
  mla: Emtenani, Shamsi, et al. “Macrophage Mitochondrial Bioenergetics and Tissue
    Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The Embo Journal</i>,
    vol. 41, e109049, Embo Press, 2022, doi:<a href="https://doi.org/10.15252/embj.2021109049">10.15252/embj.2021109049</a>.
  short: S. Emtenani, E.T. Martin, A. György, J. Bicher, J.-W. Genger, T. Köcher,
    M. Akhmanova, M. Pereira Guarda, M. Roblek, A. Bergthaler, T.R. Hurd, P. Rangan,
    D.E. Siekhaus, The Embo Journal 41 (2022).
date_created: 2022-03-24T13:23:09Z
date_published: 2022-03-23T00:00:00Z
date_updated: 2023-08-03T06:13:14Z
day: '23'
ddc:
- '570'
department:
- _id: DaSi
- _id: LoSw
doi: 10.15252/embj.2021109049
ec_funded: 1
external_id:
  isi:
  - '000771957000001'
file:
- access_level: open_access
  checksum: dba48580fe0fefaa4c63078d1d2a35df
  content_type: application/pdf
  creator: siekhaus
  date_created: 2022-03-24T13:22:41Z
  date_updated: 2022-03-24T13:22:41Z
  file_id: '10919'
  file_name: Macrophage mitochondrial bioenergetics and tissue invasion are boosted
    by an Atossa-Porthos axis in Drosopila.pdf
  file_size: 4344585
  relation: main_file
file_date_updated: 2022-03-24T13:22:41Z
has_accepted_license: '1'
intvolume: '        41'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2536F660-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
- _id: 264CBBAC-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: M02379
  name: Modeling epithelial tissue mechanics during cell invasion
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
publication: The Embo Journal
publication_identifier:
  eissn:
  - 1460-2075
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an
  Atossa-Porthos axis in Drosophila
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 41
year: '2022'
...
---
_id: '9363'
abstract:
- lang: eng
  text: Optogenetics has been harnessed to shed new mechanistic light on current and
    future therapeutic strategies. This has been to date achieved by the regulation
    of ion flow and electrical signals in neuronal cells and neural circuits that
    are known to be affected by disease. In contrast, the optogenetic delivery of
    trophic biochemical signals, which support cell survival and are implicated in
    degenerative disorders, has never been demonstrated in an animal model of disease.
    Here, we reengineered the human and Drosophila melanogaster REarranged during
    Transfection (hRET and dRET) receptors to be activated by light, creating one-component
    optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation,
    these receptors robustly induced the MAPK/ERK proliferative signaling pathway
    in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative
    kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD),
    light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration
    and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial
    fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results
    demonstrate that a light-activated receptor can ameliorate disease hallmarks in
    a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific
    and reversible and thus has the potential to inspire novel strategies towards
    a spatio-temporal regulation of tissue repair.
acknowledgement: We thank R. Cagan, A. Whitworth and J. Nagpal for fly lines and advice,
  S. Herlitze for provision of a tissue culture illuminator, and Verian Bader for
  help with statistical analysis.
article_processing_charge: No
author:
- first_name: Álvaro
  full_name: Inglés Prieto, Álvaro
  id: 2A9DB292-F248-11E8-B48F-1D18A9856A87
  last_name: Inglés Prieto
  orcid: 0000-0002-5409-8571
- first_name: Nikolas
  full_name: Furthmann, Nikolas
  last_name: Furthmann
- first_name: Samuel H.
  full_name: Crossman, Samuel H.
  last_name: Crossman
- first_name: Alexandra Madelaine
  full_name: Tichy, Alexandra Madelaine
  last_name: Tichy
- first_name: Nina
  full_name: Hoyer, Nina
  last_name: Hoyer
- first_name: Meike
  full_name: Petersen, Meike
  last_name: Petersen
- first_name: Vanessa
  full_name: Zheden, Vanessa
  id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
  last_name: Zheden
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Eva
  full_name: Gschaider-Reichhart, Eva
  id: 3FEE232A-F248-11E8-B48F-1D18A9856A87
  last_name: Gschaider-Reichhart
  orcid: 0000-0002-7218-7738
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
- first_name: Peter
  full_name: Soba, Peter
  last_name: Soba
- first_name: Konstanze F.
  full_name: Winklhofer, Konstanze F.
  last_name: Winklhofer
- first_name: Harald L
  full_name: Janovjak, Harald L
  id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
  last_name: Janovjak
  orcid: 0000-0002-8023-9315
citation:
  ama: Inglés Prieto Á, Furthmann N, Crossman SH, et al. Optogenetic delivery of trophic
    signals in a genetic model of Parkinson’s disease. <i>PLoS genetics</i>. 2021;17(4):e1009479.
    doi:<a href="https://doi.org/10.1371/journal.pgen.1009479">10.1371/journal.pgen.1009479</a>
  apa: Inglés Prieto, Á., Furthmann, N., Crossman, S. H., Tichy, A. M., Hoyer, N.,
    Petersen, M., … Janovjak, H. L. (2021). Optogenetic delivery of trophic signals
    in a genetic model of Parkinson’s disease. <i>PLoS Genetics</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pgen.1009479">https://doi.org/10.1371/journal.pgen.1009479</a>
  chicago: Inglés Prieto, Álvaro, Nikolas Furthmann, Samuel H. Crossman, Alexandra
    Madelaine Tichy, Nina Hoyer, Meike Petersen, Vanessa Zheden, et al. “Optogenetic
    Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” <i>PLoS
    Genetics</i>. Public Library of Science, 2021. <a href="https://doi.org/10.1371/journal.pgen.1009479">https://doi.org/10.1371/journal.pgen.1009479</a>.
  ieee: Á. Inglés Prieto <i>et al.</i>, “Optogenetic delivery of trophic signals in
    a genetic model of Parkinson’s disease,” <i>PLoS genetics</i>, vol. 17, no. 4.
    Public Library of Science, p. e1009479, 2021.
  ista: Inglés Prieto Á, Furthmann N, Crossman SH, Tichy AM, Hoyer N, Petersen M,
    Zheden V, Bicher J, Gschaider-Reichhart E, György A, Siekhaus DE, Soba P, Winklhofer
    KF, Janovjak HL. 2021. Optogenetic delivery of trophic signals in a genetic model
    of Parkinson’s disease. PLoS genetics. 17(4), e1009479.
  mla: Inglés Prieto, Álvaro, et al. “Optogenetic Delivery of Trophic Signals in a
    Genetic Model of Parkinson’s Disease.” <i>PLoS Genetics</i>, vol. 17, no. 4, Public
    Library of Science, 2021, p. e1009479, doi:<a href="https://doi.org/10.1371/journal.pgen.1009479">10.1371/journal.pgen.1009479</a>.
  short: Á. Inglés Prieto, N. Furthmann, S.H. Crossman, A.M. Tichy, N. Hoyer, M. Petersen,
    V. Zheden, J. Bicher, E. Gschaider-Reichhart, A. György, D.E. Siekhaus, P. Soba,
    K.F. Winklhofer, H.L. Janovjak, PLoS Genetics 17 (2021) e1009479.
date_created: 2021-05-02T22:01:29Z
date_published: 2021-04-01T00:00:00Z
date_updated: 2023-08-08T13:17:47Z
day: '01'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: LoSw
- _id: DaSi
doi: 10.1371/journal.pgen.1009479
external_id:
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  - '000640606700001'
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month: '04'
oa: 1
oa_version: Published Version
page: e1009479
publication: PLoS genetics
publication_identifier:
  eissn:
  - '15537404'
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
  text: Mosaic analysis with double markers (MADM) offers one approach to visualize
    and concomitantly manipulate genetically defined cells in mice with single-cell
    resolution. MADM applications include the analysis of lineage, single-cell morphology
    and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
    gene functions in vivo in health and disease. Yet, MADM can only be applied to
    <25% of all mouse genes on select chromosomes to date. To overcome this limitation,
    we generate transgenic mice with knocked-in MADM cassettes near the centromeres
    of all 19 autosomes and validate their use across organs. With this resource,
    >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
    analysis. Beyond a proof of principle, we apply our MADM library to systematically
    trace sister chromatid segregation in distinct mitotic cell lineages. We find
    striking chromosome-specific biases in segregation patterns, reflecting a putative
    mechanism for the asymmetric segregation of genetic determinants in somatic stem
    cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
  at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
  M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
  R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
  the Hippenmeyer lab for discussion. This work was supported by National Institutes
  of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
  of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
  a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
  work also received support from IST Austria institutional funds , FWF SFB F78 to
  S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
  Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
  and the European Research Council (ERC) under the European Union’s Horizon 2020
  Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
  full_name: Davaatseren, Amarbayasgalan
  id: 70ADC922-B424-11E9-99E3-BA18E6697425
  last_name: Davaatseren
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Johanna
  full_name: Sonntag, Johanna
  id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
  last_name: Sonntag
- first_name: Lill
  full_name: Andersen, Lill
  last_name: Andersen
- first_name: Tina
  full_name: Bernthaler, Tina
  last_name: Bernthaler
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Anna-Magdalena
  full_name: Heger, Anna-Magdalena
  id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
  last_name: Heger
- first_name: Randy L.
  full_name: Johnson, Randy L.
  last_name: Johnson
- first_name: Lindsay A.
  full_name: Schwarz, Lindsay A.
  last_name: Schwarz
- first_name: Liqun
  full_name: Luo, Liqun
  last_name: Luo
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
    mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12).
    doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>
  apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
    L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>
  chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
    Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
    of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell
    Press, 2021. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>.
  ieee: X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.
  ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
    T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
    S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
    Cell Reports. 35(12), 109274.
  mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
    Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press,
    2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>.
  short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
    T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
    T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
  isi:
  - '000664463600016'
file:
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file_date_updated: 2021-06-28T14:06:24Z
has_accepted_license: '1'
intvolume: '        35'
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language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
  eissn:
  - '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
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    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '8914'
abstract:
- lang: eng
  text: Amyotrophic lateral sclerosis (ALS) leads to a loss of specific motor neuron
    populations in the spinal cord and cortex. Emerging evidence suggests that interneurons
    may also be affected, but a detailed characterization of interneuron loss and
    its potential impacts on motor neuron loss and disease progression is lacking.
    To examine this issue, the fate of V1 inhibitory neurons during ALS was assessed
    in the ventral spinal cord using the SODG93A mouse model. The V1 population makes
    up ∼30% of all ventral inhibitory neurons, ∼50% of direct inhibitory synaptic
    contacts onto motor neuron cell bodies, and is thought to play a key role in modulating
    motor output, in part through recurrent and reciprocal inhibitory circuits. We
    find that approximately half of V1 inhibitory neurons are lost in SODG93A mice
    at late disease stages, but that this loss is delayed relative to the loss of
    motor neurons and V2a excitatory neurons. We further identify V1 subpopulations
    based on transcription factor expression that are differentially susceptible to
    degeneration in SODG93A mice. At an early disease stage, we show that V1 synaptic
    contacts with motor neuron cell bodies increase, suggesting an upregulation of
    inhibition before V1 neurons are lost in substantial numbers. These data support
    a model in which progressive changes in V1 synaptic contacts early in disease,
    and in select V1 subpopulations at later stages, represent a compensatory upregulation
    and then deleterious breakdown of specific interneuron circuits within the spinal
    cord.
acknowledgement: This work was made possible by the generous support of Project ALS.
  Imaging and related analyses were facilitated by The Waitt Advanced Biophotonics
  Center Core at the Salk Institute, supported by grants from NIH-NCI CCSG (P30 014195)
  and NINDS Neuroscience Center (NS072031). The authors would like to additionally
  thank Drs. Jane Dodd, Robert Brownstone, and Laskaro Zagoraiou for helpful comments
  on the manuscript. This manuscript is dedicated to Tom Jessell, an inspirational
  scientist, friend and mentor.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Alina
  full_name: Salamatina, Alina
  last_name: Salamatina
- first_name: Jerry H
  full_name: Yang, Jerry H
  last_name: Yang
- first_name: Susan
  full_name: Brenner-Morton, Susan
  last_name: Brenner-Morton
- first_name: 'Jay B '
  full_name: 'Bikoff, Jay B '
  last_name: Bikoff
- first_name: Linjing
  full_name: Fang, Linjing
  last_name: Fang
- first_name: Christopher R
  full_name: Kintner, Christopher R
  last_name: Kintner
- first_name: Thomas M
  full_name: Jessell, Thomas M
  last_name: Jessell
- first_name: Lora Beatrice Jaeger
  full_name: Sweeney, Lora Beatrice Jaeger
  id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
  last_name: Sweeney
  orcid: 0000-0001-9242-5601
citation:
  ama: Salamatina A, Yang JH, Brenner-Morton S, et al. Differential loss of spinal
    interneurons in a mouse model of ALS. <i>Neuroscience</i>. 2020;450:81-95. doi:<a
    href="https://doi.org/10.1016/j.neuroscience.2020.08.011">10.1016/j.neuroscience.2020.08.011</a>
  apa: Salamatina, A., Yang, J. H., Brenner-Morton, S., Bikoff, J. B., Fang, L., Kintner,
    C. R., … Sweeney, L. B. (2020). Differential loss of spinal interneurons in a
    mouse model of ALS. <i>Neuroscience</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuroscience.2020.08.011">https://doi.org/10.1016/j.neuroscience.2020.08.011</a>
  chicago: Salamatina, Alina, Jerry H Yang, Susan Brenner-Morton, Jay B  Bikoff, Linjing
    Fang, Christopher R Kintner, Thomas M Jessell, and Lora B. Sweeney. “Differential
    Loss of Spinal Interneurons in a Mouse Model of ALS.” <i>Neuroscience</i>. Elsevier,
    2020. <a href="https://doi.org/10.1016/j.neuroscience.2020.08.011">https://doi.org/10.1016/j.neuroscience.2020.08.011</a>.
  ieee: A. Salamatina <i>et al.</i>, “Differential loss of spinal interneurons in
    a mouse model of ALS,” <i>Neuroscience</i>, vol. 450. Elsevier, pp. 81–95, 2020.
  ista: Salamatina A, Yang JH, Brenner-Morton S, Bikoff JB, Fang L, Kintner CR, Jessell
    TM, Sweeney LB. 2020. Differential loss of spinal interneurons in a mouse model
    of ALS. Neuroscience. 450, 81–95.
  mla: Salamatina, Alina, et al. “Differential Loss of Spinal Interneurons in a Mouse
    Model of ALS.” <i>Neuroscience</i>, vol. 450, Elsevier, 2020, pp. 81–95, doi:<a
    href="https://doi.org/10.1016/j.neuroscience.2020.08.011">10.1016/j.neuroscience.2020.08.011</a>.
  short: A. Salamatina, J.H. Yang, S. Brenner-Morton, J.B. Bikoff, L. Fang, C.R. Kintner,
    T.M. Jessell, L.B. Sweeney, Neuroscience 450 (2020) 81–95.
date_created: 2020-12-03T11:47:31Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-01-31T10:15:34Z
day: '01'
ddc:
- '570'
department:
- _id: LoSw
doi: 10.1016/j.neuroscience.2020.08.011
external_id:
  isi:
  - '000595588700008'
  pmid:
  - '32858144'
file:
- access_level: open_access
  checksum: da7413c819e079720669c82451b49294
  content_type: application/pdf
  creator: dernst
  date_created: 2020-12-03T11:45:26Z
  date_updated: 2020-12-03T11:45:26Z
  file_id: '8915'
  file_name: 2020_Neuroscience_Salamatina.pdf
  file_size: 4071247
  relation: main_file
  success: 1
file_date_updated: 2020-12-03T11:45:26Z
has_accepted_license: '1'
intvolume: '       450'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 81-95
pmid: 1
publication: Neuroscience
publication_identifier:
  issn:
  - 0306-4522
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Differential loss of spinal interneurons in a mouse model of ALS
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 450
year: '2020'
...
