A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism

Lorenzo Rella; Euclides E Fernandes Póvoa; Jonas Mars; Annabel L P Ebbing; Luc Schoppink; Marco C Betist; Hendrik C Korswagen

doi:10.1073/pnas.2013239118

A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism

Lorenzo Rella, Euclides E Fernandes Póvoa, Jonas Mars, Annabel L P Ebbing, Luc Schoppink, Marco C Betist, Hendrik C Korswagen^*

^*Corresponding author for this work

Hubrecht Institute

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.

Original language	English
Article number	e2013239118
Pages (from-to)	1-12
Number of pages	12
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	12
DOIs	https://doi.org/10.1073/pnas.2013239118
Publication status	Published - 18 Mar 2021

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Stefan van der Elst from the Flow Cytometry Core facility and the Hubrecht Imaging Center (Hubrecht Institute) for technical support, and Guangshuo Ou (Tsinghua University, Beijing, China) and Barbara Conradt (University College London, United Kingdom) for reagents. Part of this work was funded by the research program (14NOISE01) of the Foundation for Fundamental Research on Matter, which is financially supported by the Netherlands Organization for Scientific Research. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We are grateful to members of the Korswagen and Galli groups for helpful discussions and critical reading of the manuscript.

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.

Keywords

C. elegans
Cell migration
Pathway interactions
Slt-Robo
Wnt

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10.1073/pnas.2013239118

e2013239118.fullFinal published version, 2.78 MBLicence: Taverne

Cite this

Rella, L., Fernandes Póvoa, E. E., Mars, J., Ebbing, A. L. P., Schoppink, L., Betist, M. C., & Korswagen, H. C. (2021). A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism. Proceedings of the National Academy of Sciences of the United States of America, 118(12), 1-12. Article e2013239118. https://doi.org/10.1073/pnas.2013239118

@article{d1e83d9ccbf94d9585ce6b470d8008d5,

title = "A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism",

abstract = "Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.",

keywords = "C. elegans, Cell migration, Pathway interactions, Slt-Robo, Wnt",

author = "Lorenzo Rella and {Fernandes P{\'o}voa}, {Euclides E} and Jonas Mars and Ebbing, {Annabel L P} and Luc Schoppink and Betist, {Marco C} and Korswagen, {Hendrik C}",

note = "Funding Information: ACKNOWLEDGMENTS. We thank Stefan van der Elst from the Flow Cytometry Core facility and the Hubrecht Imaging Center (Hubrecht Institute) for technical support, and Guangshuo Ou (Tsinghua University, Beijing, China) and Barbara Conradt (University College London, United Kingdom) for reagents. Part of this work was funded by the research program (14NOISE01) of the Foundation for Fundamental Research on Matter, which is financially supported by the Netherlands Organization for Scientific Research. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We are grateful to members of the Korswagen and Galli groups for helpful discussions and critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",

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Rella, L, Fernandes Póvoa, EE, Mars, J, Ebbing, ALP, Schoppink, L, Betist, MC & Korswagen, HC 2021, 'A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 12, e2013239118, pp. 1-12. https://doi.org/10.1073/pnas.2013239118

A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism. / Rella, Lorenzo; Fernandes Póvoa, Euclides E; Mars, Jonas et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, No. 12, e2013239118, 18.03.2021, p. 1-12.

Research output: Contribution to journal › Article › Academic › peer-review

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AU - Fernandes Póvoa, Euclides E

AU - Mars, Jonas

AU - Ebbing, Annabel L P

AU - Schoppink, Luc

AU - Betist, Marco C

AU - Korswagen, Hendrik C

N1 - Funding Information: ACKNOWLEDGMENTS. We thank Stefan van der Elst from the Flow Cytometry Core facility and the Hubrecht Imaging Center (Hubrecht Institute) for technical support, and Guangshuo Ou (Tsinghua University, Beijing, China) and Barbara Conradt (University College London, United Kingdom) for reagents. Part of this work was funded by the research program (14NOISE01) of the Foundation for Fundamental Research on Matter, which is financially supported by the Netherlands Organization for Scientific Research. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We are grateful to members of the Korswagen and Galli groups for helpful discussions and critical reading of the manuscript. Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.

PY - 2021/3/18

Y1 - 2021/3/18

N2 - Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.

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KW - Pathway interactions

KW - Slt-Robo

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SN - 0027-8424

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JF - Proceedings of the National Academy of Sciences of the United States of America

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M1 - e2013239118

ER -

A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism

Abstract

Bibliographical note

Keywords

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