---
_id: '6025'
abstract:
- lang: eng
text: Non-canonical Wnt signaling plays a central role for coordinated cell polarization
and directed migration in metazoan development. While spatiotemporally restricted
activation of non-canonical Wnt-signaling drives cell polarization in epithelial
tissues, it remains unclear whether such instructive activity is also critical
for directed mesenchymal cell migration. Here, we developed a light-activated
version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted
activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm
(prechordal plate, ppl) cell migration within the zebrafish gastrula. We found
that Fz7 signaling is required for ppl cell protrusion formation and migration
and that spatiotemporally restricted ectopic activation is capable of redirecting
their migration. Finally, we show that uniform activation of Fz7 signaling in
ppl cells fully rescues defective directed cell migration in fz7 mutant embryos.
Together, our findings reveal that in contrast to the situation in epithelial
cells, non-canonical Wnt signaling functions permissively rather than instructively
in directed mesenchymal cell migration during gastrulation.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
article_number: e42093
article_processing_charge: No
author:
- first_name: Daniel
full_name: Capek, Daniel
id: 31C42484-F248-11E8-B48F-1D18A9856A87
last_name: Capek
orcid: 0000-0001-5199-9940
- first_name: Michael
full_name: Smutny, Michael
id: 3FE6E4E8-F248-11E8-B48F-1D18A9856A87
last_name: Smutny
orcid: 0000-0002-5920-9090
- first_name: Alexandra Madelaine
full_name: Tichy, Alexandra Madelaine
last_name: Tichy
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated
Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm
cell migration. eLife. 2019;8. doi:10.7554/eLife.42093
apa: Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., & Heisenberg,
C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical
wnt signaling in mesendoderm cell migration. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.42093
chicago: Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri,
Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals
a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.”
ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42093.
ieee: D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg,
“Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration,” eLife, vol. 8. eLife Sciences Publications,
2019.
ista: Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019.
Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration. eLife. 8, e42093.
mla: Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role
of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife, vol.
8, e42093, eLife Sciences Publications, 2019, doi:10.7554/eLife.42093.
short: D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg,
ELife 8 (2019).
date_created: 2019-02-17T22:59:22Z
date_published: 2019-02-06T00:00:00Z
date_updated: 2023-08-24T14:46:01Z
day: '06'
ddc:
- '570'
department:
- _id: CaHe
- _id: HaJa
doi: 10.7554/eLife.42093
ec_funded: 1
external_id:
isi:
- '000458025300001'
file:
- access_level: open_access
checksum: 6cb4ca6d4aa96f6f187a5983aa3e660a
content_type: application/pdf
creator: dernst
date_created: 2019-02-18T15:17:21Z
date_updated: 2020-07-14T12:47:17Z
file_id: '6041'
file_name: 2019_elife_Capek.pdf
file_size: 5500707
relation: main_file
file_date_updated: 2020-07-14T12:47:17Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling
in mesendoderm cell migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2019'
...
---
_id: '5984'
abstract:
- lang: eng
text: G-protein-coupled receptors (GPCRs) form the largest receptor family, relay
environmental stimuli to changes in cell behavior and represent prime drug targets.
Many GPCRs are classified as orphan receptors because of the limited knowledge
on their ligands and coupling to cellular signaling machineries. Here, we engineer
a library of 63 chimeric receptors that contain the signaling domains of human
orphan and understudied GPCRs functionally linked to the light-sensing domain
of rhodopsin. Upon stimulation with visible light, we identify activation of canonical
cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent
pathways, downstream of the engineered receptors. For the human pseudogene GPR33,
we resurrect a signaling function that supports its hypothesized role as a pathogen
entry site. These results demonstrate that substituting unknown chemical activators
with a light switch can reveal information about protein function and provide
an optically controlled protein library for exploring the physiology and therapeutic
potential of understudied GPCRs.
article_number: '1950'
article_processing_charge: No
author:
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
- first_name: Inmaculada
full_name: Sanchez-Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez-Romero
- first_name: Alexandra-Madelaine
full_name: Tichy, Alexandra-Madelaine
id: 29D8BB2C-F248-11E8-B48F-1D18A9856A87
last_name: Tichy
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
- first_name: Elliot J.
full_name: Gerrard, Elliot J.
last_name: Gerrard
- first_name: Priscila
full_name: Hirschfeld, Priscila
id: 435ACB3A-F248-11E8-B48F-1D18A9856A87
last_name: Hirschfeld
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- 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: Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human
class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1).
doi:10.1038/s41467-018-04342-1
apa: Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J.,
Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class
A orphan G-protein-coupled receptors. Nature Communications. Springer Nature.
https://doi.org/10.1038/s41467-018-04342-1
chicago: Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy,
Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald
L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled
Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1.
ieee: M. Morri et al., “Optical functionalization of human class A orphan
G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer
Nature, 2018.
ista: Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P,
Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan
G-protein-coupled receptors. Nature Communications. 9(1), 1950.
mla: Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan
G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950,
Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.
short: M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld,
J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).
date_created: 2019-02-14T10:50:24Z
date_published: 2018-12-01T00:00:00Z
date_updated: 2023-09-19T14:29:32Z
day: '01'
ddc:
- '570'
department:
- _id: HaJa
- _id: CaGu
- _id: MiSi
doi: 10.1038/s41467-018-04342-1
ec_funded: 1
external_id:
isi:
- '000432280000006'
file:
- access_level: open_access
checksum: 8325fcc194264af4749e662a73bf66b5
content_type: application/pdf
creator: kschuh
date_created: 2019-02-14T10:58:29Z
date_updated: 2020-07-14T12:47:14Z
file_id: '5985'
file_name: 2018_Springer_Morri.pdf
file_size: 1349914
relation: main_file
file_date_updated: 2020-07-14T12:47:14Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303564'
name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 255A6082-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optical functionalization of human class A orphan G-protein-coupled receptors
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 9
year: '2018'
...
---
_id: '1124'
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
citation:
ama: Morri M. Optical functionalization of human class A orphan G-protein coupled
receptors. 2016.
apa: Morri, M. (2016). Optical functionalization of human class A orphan G-protein
coupled receptors. Institute of Science and Technology Austria.
chicago: Morri, Maurizio. “Optical Functionalization of Human Class A Orphan G-Protein
Coupled Receptors.” Institute of Science and Technology Austria, 2016.
ieee: M. Morri, “Optical functionalization of human class A orphan G-protein coupled
receptors,” Institute of Science and Technology Austria, 2016.
ista: Morri M. 2016. Optical functionalization of human class A orphan G-protein
coupled receptors. Institute of Science and Technology Austria.
mla: Morri, Maurizio. Optical Functionalization of Human Class A Orphan G-Protein
Coupled Receptors. Institute of Science and Technology Austria, 2016.
short: M. Morri, Optical Functionalization of Human Class A Orphan G-Protein Coupled
Receptors, Institute of Science and Technology Austria, 2016.
date_created: 2018-12-11T11:50:17Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2023-09-07T11:43:03Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: HaJa
file:
- access_level: closed
checksum: b439803ac0827cdddd56562a54e3b53b
content_type: application/pdf
creator: dernst
date_created: 2019-08-13T10:50:00Z
date_updated: 2019-08-13T10:50:00Z
file_id: '6812'
file_name: MORRI_PhD_thesis_FINALPLUSSIGNATURES (2).pdf
file_size: 4785167
relation: main_file
- access_level: open_access
checksum: dd4136247fe472e7d47880ec68ac8de0
content_type: application/pdf
creator: dernst
date_created: 2021-02-22T11:42:06Z
date_updated: 2021-02-22T11:42:06Z
file_id: '9180'
file_name: 2016_MORRI_Thesis.pdf
file_size: 4495669
relation: main_file
success: 1
file_date_updated: 2021-02-22T11:42:06Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '129'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6236'
status: public
supervisor:
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
title: Optical functionalization of human class A orphan G-protein coupled receptors
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2016'
...