---
_id: '11193'
abstract:
- lang: eng
  text: "The infiltration of immune cells into tissues underlies the establishment
    of tissue-resident\r\nmacrophages and responses to infections and tumors. However,
    the mechanisms immune\r\ncells utilize to collectively migrate through tissue
    barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two
    mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue
    barrier of the germband in the embryo. One strategy is the strengthening\r\nof
    the actin cortex through developmentally controlled transcriptional regulation
    induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in
    Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin
    Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and
    increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes
    to overcome the physical resistance of the surrounding tissue and\r\ntranslocate
    their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen
    hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion
    process is the initial step of the leading hemocytes entering\r\nthe tissue, which
    potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation
    of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration
    into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow
    impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis
    suggests that there might be different mechanisms controlling immune cell migration\r\nwithin
    the confined environment in vivo, one of these being the general ability to overcome\r\nthe
    resistance of the surrounding tissue and another affecting the order of hemocytes
    that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether,
    my findings provide deeper insights into transcriptional changes in immune\r\ncells
    that enable efficient tissue invasion and pave the way for future studies investigating
    the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover,
    they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point
    toward a potentially\r\nconserved role for canonical BMP signaling in specifying
    immune cells that lead the migration\r\nof tissue resident macrophages during
    embryogenesis."
acknowledged_ssus:
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
  full_name: Wachner, Stephanie
  id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
  last_name: Wachner
citation:
  ama: Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue
    invasion of Drosophila immune cells. 2022. doi:<a href="https://doi.org/10.15479/at:ista:11193">10.15479/at:ista:11193</a>
  apa: Wachner, S. (2022). <i>Transcriptional regulation by Dfos and BMP-signaling
    support tissue invasion of Drosophila immune cells</i>. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/at:ista:11193">https://doi.org/10.15479/at:ista:11193</a>
  chicago: Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling
    Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and
    Technology Austria, 2022. <a href="https://doi.org/10.15479/at:ista:11193">https://doi.org/10.15479/at:ista:11193</a>.
  ieee: S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support
    tissue invasion of Drosophila immune cells,” Institute of Science and Technology
    Austria, 2022.
  ista: Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support
    tissue invasion of Drosophila immune cells. Institute of Science and Technology
    Austria.
  mla: Wachner, Stephanie. <i>Transcriptional Regulation by Dfos and BMP-Signaling
    Support Tissue Invasion of Drosophila Immune Cells</i>. Institute of Science and
    Technology Austria, 2022, doi:<a href="https://doi.org/10.15479/at:ista:11193">10.15479/at:ista:11193</a>.
  short: S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support
    Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology
    Austria, 2022.
date_created: 2022-04-20T08:59:07Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
day: '20'
ddc:
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degree_awarded: PhD
department:
- _id: GradSch
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doi: 10.15479/at:ista:11193
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publisher: Institute of Science and Technology Austria
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    status: public
status: public
supervisor:
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
title: Transcriptional regulation by Dfos and BMP-signaling support tissue invasion
  of Drosophila immune cells
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: '2022'
...
---
_id: '10614'
abstract:
- lang: eng
  text: 'The infiltration of immune cells into tissues underlies the establishment
    of tissue-resident macrophages and responses to infections and tumors. Yet the
    mechanisms immune cells utilize to negotiate tissue barriers in living organisms
    are not well understood, and a role for cortical actin has not been examined.
    Here, we find that the tissue invasion of Drosophila macrophages, also known as
    plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
    by the Drosophila member of the fos proto oncogene transcription factor family
    (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
    F-actin levels around the entire macrophage surface by increasing mRNA levels
    of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
    filamin Cheerio, which are themselves required for invasion. Both the filamin
    and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous
    and thus the assembly of cortical actin, which is a critical function since expressing
    a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect.
    In vivo imaging shows that Dfos enhances the efficiency of the initial phases
    of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
    in macrophages counteracts the constraint produced by the tension of surrounding
    tissues and buffers the properties of the macrophage nucleus from affecting tissue
    entry. We thus identify strengthening the cortical actin cytoskeleton through
    Dfos as a key process allowing efficient forward movement of an immune cell into
    surrounding tissues. '
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: Plasmids were supplied
  by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were
  provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington
  Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center,
  FlyBase for essential genomic information, and the BDGP in situ database for data.
  For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created
  by the Eunice Kennedy Shriver National Institute of Child Health and Human Development
  of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger
  for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities
  for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
  for technical support and assistance with microscopy and FACS analysis. We thank
  C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions
  and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.'
article_processing_charge: No
article_type: original
author:
- first_name: Vera
  full_name: Belyaeva, Vera
  id: 47F080FE-F248-11E8-B48F-1D18A9856A87
  last_name: Belyaeva
- first_name: Stephanie
  full_name: Wachner, Stephanie
  id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
  last_name: Wachner
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Shamsi
  full_name: Emtenani, Shamsi
  id: 49D32318-F248-11E8-B48F-1D18A9856A87
  last_name: Emtenani
  orcid: 0000-0001-6981-6938
- first_name: Igor
  full_name: Gridchyn, Igor
  id: 4B60654C-F248-11E8-B48F-1D18A9856A87
  last_name: Gridchyn
  orcid: 0000-0002-1807-1929
- first_name: Maria
  full_name: Akhmanova, Maria
  id: 3425EC26-F248-11E8-B48F-1D18A9856A87
  last_name: Akhmanova
  orcid: 0000-0003-1522-3162
- first_name: M
  full_name: Linder, M
  last_name: Linder
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: M
  full_name: Sibilia, M
  last_name: Sibilia
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration
    against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
    <i>PLoS Biology</i>. 2022;20(1):e3001494. doi:<a href="https://doi.org/10.1371/journal.pbio.3001494">10.1371/journal.pbio.3001494</a>
  apa: Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova,
    M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding
    tissue resistance by a cortical actin-based mechanism in Drosophila. <i>PLoS Biology</i>.
    Public Library of Science. <a href="https://doi.org/10.1371/journal.pbio.3001494">https://doi.org/10.1371/journal.pbio.3001494</a>
  chicago: Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor
    Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus.
    “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by
    a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS Biology</i>. Public Library
    of Science, 2022. <a href="https://doi.org/10.1371/journal.pbio.3001494">https://doi.org/10.1371/journal.pbio.3001494</a>.
  ieee: V. Belyaeva <i>et al.</i>, “Fos regulates macrophage infiltration against
    surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,”
    <i>PLoS Biology</i>, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.
  ista: Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder
    M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration
    against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
    PLoS Biology. 20(1), e3001494.
  mla: Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding
    Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS
    Biology</i>, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:<a
    href="https://doi.org/10.1371/journal.pbio.3001494">10.1371/journal.pbio.3001494</a>.
  short: V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova,
    M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494.
date_created: 2022-01-12T10:18:17Z
date_published: 2022-01-06T00:00:00Z
date_updated: 2024-03-25T23:30:15Z
day: '06'
ddc:
- '570'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1371/journal.pbio.3001494
ec_funded: 1
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  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
  grant_number: '24800'
  name: Tissue barrier penetration is crucial for immunity and metastasis
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  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
publication: PLoS Biology
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  issn:
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publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
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    url: https://www.biorxiv.org/content/10.1101/2020.09.18.301481
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    relation: press_release
    url: https://ista.ac.at/en/news/resisting-the-pressure/
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  - id: '11193'
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scopus_import: '1'
status: public
title: Fos regulates macrophage infiltration against surrounding tissue resistance
  by a cortical actin-based mechanism 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: 20
year: '2022'
...
---
_id: '8557'
abstract:
- lang: eng
  text: The infiltration of immune cells into tissues underlies the establishment
    of tissue resident macrophages, and responses to infections and tumors. Yet the
    mechanisms immune cells utilize to negotiate tissue barriers in living organisms
    are not well understood, and a role for cortical actin has not been examined.
    Here we find that the tissue invasion of Drosophila macrophages, also known as
    plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
    by the Drosophila member of the fos proto oncogene transcription factor family
    (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
    F-actin levels around the entire macrophage surface by increasing mRNA levels
    of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
    filamin Cheerio which are themselves required for invasion. Cortical F-actin levels
    are critical as expressing a dominant active form of Diaphanous, a actin polymerizing
    Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo
    imaging shows that Dfos is required to enhance the efficiency of the initial phases
    of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
    in macrophages counteracts the constraint produced by the tension of surrounding
    tissues and buffers the mechanical properties of the macrophage nucleus from affecting
    tissue entry. We thus identify tuning the cortical actin cytoskeleton through
    Dfos as a key process allowing efficient forward movement of an immune cell into
    surrounding tissues.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: The Drosophila Genomics
  Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner.
  B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center
  supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for
  fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and
  the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies,
  we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice
  Kennedy Shriver National Institute of Child Health and Human Development of the
  NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her
  generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for
  RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
  for technical support and assistance with microscopy and FACS analysis. We thank
  C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and
  T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported
  by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie
  CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European
  Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is
  supported by an OEAW, DOC fellowship.'
article_processing_charge: No
author:
- first_name: Vera
  full_name: Belyaeva, Vera
  id: 47F080FE-F248-11E8-B48F-1D18A9856A87
  last_name: Belyaeva
- first_name: Stephanie
  full_name: Wachner, Stephanie
  id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
  last_name: Wachner
- first_name: Igor
  full_name: Gridchyn, Igor
  id: 4B60654C-F248-11E8-B48F-1D18A9856A87
  last_name: Gridchyn
  orcid: 0000-0002-1807-1929
- first_name: Markus
  full_name: Linder, Markus
  last_name: Linder
- first_name: Shamsi
  full_name: Emtenani, Shamsi
  id: 49D32318-F248-11E8-B48F-1D18A9856A87
  last_name: Emtenani
  orcid: 0000-0001-6981-6938
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Maria
  full_name: Sibilia, Maria
  last_name: Sibilia
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled
    by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance.
    <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2020.09.18.301481">10.1101/2020.09.18.301481</a>
  apa: Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György,
    A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila
    Fos aid macrophage infiltration against surrounding tissue resistance. <i>bioRxiv</i>.
    <a href="https://doi.org/10.1101/2020.09.18.301481">https://doi.org/10.1101/2020.09.18.301481</a>
  chicago: Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi
    Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin
    Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding
    Tissue Resistance.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2020.09.18.301481">https://doi.org/10.1101/2020.09.18.301481</a>.
  ieee: V. Belyaeva <i>et al.</i>, “Cortical actin properties controlled by Drosophila
    Fos aid macrophage infiltration against surrounding tissue resistance,” <i>bioRxiv</i>.
    .
  ista: Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia
    M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage
    infiltration against surrounding tissue resistance. bioRxiv, <a href="https://doi.org/10.1101/2020.09.18.301481">10.1101/2020.09.18.301481</a>.
  mla: Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila
    Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” <i>BioRxiv</i>,
    doi:<a href="https://doi.org/10.1101/2020.09.18.301481">10.1101/2020.09.18.301481</a>.
  short: V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György,
    M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).
date_created: 2020-09-23T09:36:47Z
date_published: 2020-09-18T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '18'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1101/2020.09.18.301481
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2020.09.18.301481
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
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  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
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  name: Tissue barrier penetration is crucial for immunity and metastasis
publication: bioRxiv
publication_status: submitted
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title: Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration
  against surrounding tissue resistance
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...