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 - Fernandes Póvoa, Euclides E
AU - Mars, Jonas
AU - Ebbing, Annabel L P
AU - Schoppink, Luc
AU - Betist, Marco C
AU - Korswagen, Hendrik C
PY - 2021/3/23
Y1 - 2021/3/23
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.
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 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.
KW - Animals
KW - Caenorhabditis elegans
KW - Caenorhabditis elegans Proteins/genetics
KW - Cell Movement/genetics
KW - GTPase-Activating Proteins/metabolism
KW - Gene Expression Regulation
KW - Nerve Tissue Proteins/genetics
KW - Neural Stem Cells/cytology
KW - Receptors, Immunologic/genetics
KW - Wnt Signaling Pathway
U2 - 10.1073/pnas.2013239118
DO - 10.1073/pnas.2013239118
M3 - Article
C2 - 33737394
SN - 0027-8424
VL - 118
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
ER -