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Dissection of Xenopus laevis Neural Crest for in vitro Explant Culture or in vivo Transplantation
Published on: March 4, 2014
Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2
M Angeles Rabadán1, Antonio Herrera2, Lucia Fanlo1
1Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri i Reixac 20, Barcelona 08028, Spain.
Abstract:
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.
Insights
Neural crest cell delamination, a model for epithelial-to-mesenchymal transition (EMT), involves transient Wnt/β-catenin signaling inhibition. Scaffold proteins Dact1/2 are crucial for this process by regulating β-catenin activity.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Neural crest (NC) cell delamination is a key developmental process and a model for epithelial-to-mesenchymal transition (EMT).
- Wnt/β-catenin signaling is known to influence EMT and cell migration during development.
Purpose of the Study:
- To investigate the role of Wnt/β-catenin signaling in NC cell delamination.
- To identify the molecular mechanisms regulating Wnt/β-catenin signaling during NC delamination.
Main Methods:
- Utilized two in vivo models (Xenopus and chick embryos).
- Investigated the expression and function of Dact1 and Dact2 proteins in pre-migratory NC cells.
- Analyzed the effects of Dact1/2 on Wnt/β-catenin signaling and β-catenin subcellular localization.
Main Results:
- Wnt/β-catenin signaling is transiently inhibited during NC delamination.
- Scaffold proteins Dact1 and Dact2 are essential for NC delamination but not for migratory cell motility.
- Dact1/2 inhibit Wnt/β-catenin signaling upstream of TCF transcriptional activity by regulating β-catenin's co-activator function without affecting its stability.
Conclusions:
- Dact1 and Dact2 act as novel regulators of Wnt/β-catenin signaling during NC delamination.
- This study reveals a new mechanism controlling β-catenin activity, impacting NC cell fate and migration.
- The findings provide insights into the regulation of EMT during embryonic development.
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