TY - JOUR
T1 - A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism
AU - Rella, Lorenzo
AU - Povoa, Euclides E.Fernandes
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 longrange 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.
AB - 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 longrange 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.
KW - C. elegans
KW - Cell migration
KW - Pathway interactions
KW - Slt-Robo
KW - Wnt
UR - http://www.scopus.com/inward/record.url?scp=85103146543&partnerID=8YFLogxK
U2 - 10.1073/PNAS.2013239118
DO - 10.1073/PNAS.2013239118
M3 - Article
C2 - 33737394
AN - SCOPUS:85103146543
SN - 0027-8424
VL - 118
SP - 1
EP - 12
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
M1 - e2013239118
ER -