---
_id: '10144'
abstract:
- lang: eng
  text: FGFs and their high-affinity receptors (FGFRs) play key roles in development,
    tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their
    individual functions cannot be determined using ligand stimulation. Here, we generated
    a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by
    the major FGFR in keratinocytes. Illumination of OptoR2-expressing HEK 293T cells
    activated FGFR signaling with remarkable temporal precision and promoted cell
    migration and proliferation. In murine and human keratinocytes, OptoR2 activation
    rapidly induced the classical FGFR signaling pathways and expression of FGF target
    genes. Surprisingly, multi-level counter-regulation occurred in keratinocytes
    in vitro and in transgenic mice in vivo, including OptoR2 down-regulation and
    loss of responsiveness to light activation. These results demonstrate unexpected
    cell type-specific limitations of optogenetic FGFRs in long-term in vitro and
    in vivo settings and highlight the complex consequences of transferring optogenetic
    cell signaling tools into their relevant cellular contexts.
acknowledgement: We thank Connor Richterich and Patricia Reinert, ETH Zurich, for
  invaluable experimental help; Manuela Pérez Berlanga, University Zurich, for help
  with the confocal imaging; Lukas Fischer for help with electrical engineering; Thomas
  Hennek, Sol Taguinod, and Dr. Stephan Sonntag, EPIC Phenomics Center, ETH Zürich,
  for the generation and maintenance of K14-OptoR2 mice; and Dr. Petra Boukamp, Leibniz
  Institute, Düsseldorf, Germany, for early-passage HaCaT keratinocytes. This work
  was supported by the ETH Zurich (grant ETH-06 15-1 to S Werner and L Maddaluno),
  the Swiss National Science Foundation (grant 31003B-189364 to S Werner), and a Marie
  Curie postdoctoral fellowship from the European Union (to L Maddaluno).
article_number: e202101100
article_processing_charge: Yes
article_type: original
author:
- first_name: Theresa
  full_name: Rauschendorfer, Theresa
  last_name: Rauschendorfer
- first_name: Selina
  full_name: Gurri, Selina
  last_name: Gurri
- first_name: Irina
  full_name: Heggli, Irina
  last_name: Heggli
- first_name: Luigi
  full_name: Maddaluno, Luigi
  last_name: Maddaluno
- first_name: Michael
  full_name: Meyer, Michael
  last_name: Meyer
- 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: Harald L
  full_name: Janovjak, Harald L
  id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
  last_name: Janovjak
  orcid: 0000-0002-8023-9315
- first_name: Sabine
  full_name: Werner, Sabine
  last_name: Werner
citation:
  ama: Rauschendorfer T, Gurri S, Heggli I, et al. Acute and chronic effects of a
    light-activated FGF receptor in keratinocytes in vitro and in mice. <i>Life Science
    Alliance</i>. 2021;4(11). doi:<a href="https://doi.org/10.26508/lsa.202101100">10.26508/lsa.202101100</a>
  apa: Rauschendorfer, T., Gurri, S., Heggli, I., Maddaluno, L., Meyer, M., Inglés
    Prieto, Á., … Werner, S. (2021). Acute and chronic effects of a light-activated
    FGF receptor in keratinocytes in vitro and in mice. <i>Life Science Alliance</i>.
    Life Science Alliance. <a href="https://doi.org/10.26508/lsa.202101100">https://doi.org/10.26508/lsa.202101100</a>
  chicago: Rauschendorfer, Theresa, Selina Gurri, Irina Heggli, Luigi Maddaluno, Michael
    Meyer, Álvaro Inglés Prieto, Harald L Janovjak, and Sabine Werner. “Acute and
    Chronic Effects of a Light-Activated FGF Receptor in Keratinocytes in Vitro and
    in Mice.” <i>Life Science Alliance</i>. Life Science Alliance, 2021. <a href="https://doi.org/10.26508/lsa.202101100">https://doi.org/10.26508/lsa.202101100</a>.
  ieee: T. Rauschendorfer <i>et al.</i>, “Acute and chronic effects of a light-activated
    FGF receptor in keratinocytes in vitro and in mice,” <i>Life Science Alliance</i>,
    vol. 4, no. 11. Life Science Alliance, 2021.
  ista: Rauschendorfer T, Gurri S, Heggli I, Maddaluno L, Meyer M, Inglés Prieto Á,
    Janovjak HL, Werner S. 2021. Acute and chronic effects of a light-activated FGF
    receptor in keratinocytes in vitro and in mice. Life Science Alliance. 4(11),
    e202101100.
  mla: Rauschendorfer, Theresa, et al. “Acute and Chronic Effects of a Light-Activated
    FGF Receptor in Keratinocytes in Vitro and in Mice.” <i>Life Science Alliance</i>,
    vol. 4, no. 11, e202101100, Life Science Alliance, 2021, doi:<a href="https://doi.org/10.26508/lsa.202101100">10.26508/lsa.202101100</a>.
  short: T. Rauschendorfer, S. Gurri, I. Heggli, L. Maddaluno, M. Meyer, Á. Inglés
    Prieto, H.L. Janovjak, S. Werner, Life Science Alliance 4 (2021).
date_created: 2021-10-17T22:01:16Z
date_published: 2021-09-21T00:00:00Z
date_updated: 2022-08-31T14:01:56Z
day: '21'
ddc:
- '576'
doi: 10.26508/lsa.202101100
extern: '1'
external_id:
  pmid:
  - '34548382'
file:
- access_level: open_access
  checksum: 89fb95b211dbe8678809e7cca4626952
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-10-18T14:48:06Z
  date_updated: 2021-10-18T14:48:06Z
  file_id: '10152'
  file_name: 2021_LifeScAlliance_Rauschendorfer.pdf
  file_size: 2055981
  relation: main_file
  success: 1
file_date_updated: 2021-10-18T14:48:06Z
has_accepted_license: '1'
intvolume: '         4'
issue: '11'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Life Science Alliance
publication_identifier:
  eissn:
  - 2575-1077
publication_status: published
publisher: Life Science Alliance
quality_controlled: '1'
scopus_import: '1'
status: public
title: Acute and chronic effects of a light-activated FGF receptor in keratinocytes
  in vitro and in mice
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2021'
...