Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.
Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination.
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/ Baldiri i Reixac 20, Barcelona 08028, Spain.
M Angeles
MA
Rabadán
Department of Cell Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, Spain.
Antonio
A
Herrera
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/ Baldiri i Reixac 20, Barcelona 08028, Spain.
Lucia
L
Fanlo
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/ Baldiri i Reixac 20, Barcelona 08028, Spain.
Susana
S
Usieto
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Carlos
C
Carmona-Fontaine
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Elias H
EH
Barriga
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Roberto
R
Mayor
Department of Cell Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, Spain.
Sebastián
S
Pons
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientíﬁc de Barcelona, C/ Baldiri i Reixac 20, Barcelona 08028, Spain emgbmc@ibmb.csic.es.
Elisa
0000-0002-0411-0069
E
Martí
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002642:Chick Embryo; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051153:Wnt Proteins; D051176:beta Catenin
Chick embryo; Dapper; Dishevelled antagonist of β-catenin; Frodo; Nuclear bodies; Xenopus embryo; β-catenin