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Published on: November 10, 2023
The dishevelled associated activator of morphogenesis protein 2 (Daam2) regulates neural tube closure
Kaushik Nama1, Baihao Su1, Jonathan Marquez2
1Department of Biology, Temple University, Philadelphia, Pennsylvania, USA.
Background:
The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and stem cell homeostasis. Modulation of the actin cytoskeleton via the non-canonical Wnt pathway regulate cell polarity and cell migration that are required for proper vertebrate gastrulation and subsequent neurulation. However, the mechanism(s) of how the non-canonical pathway mediates actin cytoskeleton modulation is not fully understood.
Results:
Herein, we characterize the role of the Formin-homology protein; dishevelled associated activator of morphogenesis 2 (Daam2) protein in the Wnt signaling pathway. Co-immunoprecipitation assays confirm the binding of Daam2 to dishevelled2 (Dvl2) as well as the domains within these proteins required for interaction; additionally, the interaction between Daam2 and Dvl2 was Wnt-regulated. Sub-cellular localization studies reveal Daam2 is cytoplasmic and regulates the cellular actin cytoskeleton by modulating actin filament formation. During Xenopus development, a knockdown or loss of Daam2 specifically produces neural tube closure defects indicative of a role in non-canonical signaling. Additionally, our studies did not identify any role for Daam2 in canonical Wnt signaling in mammalian culture cells or the Xenopus embryo.
Conclusions:
Our studies together identify Daam2 as a component of the non-canonical Wnt pathway and Daam2 is a regulator of neural tube morphogenesis during vertebrate development.
Insights
Dishevelled associated activator of morphogenesis 2 (Daam2) regulates the actin cytoskeleton via the non-canonical Wnt pathway, impacting neural tube development in vertebrates.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- The Wnt signaling pathway is crucial for conserved cellular processes in metazoans.
- Non-canonical Wnt pathways modulate the actin cytoskeleton, affecting cell polarity and migration during vertebrate development.
- Mechanisms of non-canonical Wnt pathway-mediated actin cytoskeleton modulation remain incompletely understood.
Purpose of the Study:
- To investigate the role of Formin-homology protein, dishevelled associated activator of morphogenesis 2 (Daam2), in the Wnt signaling pathway.
- To elucidate Daam2's function in actin cytoskeleton regulation and its impact on vertebrate development.
Main Methods:
- Co-immunoprecipitation assays to confirm Daam2 and dishevelled2 (Dvl2) binding and interaction domains.
- Sub-cellular localization studies to determine Daam2's cellular location and effect on actin.
- Knockdown studies in Xenopus to assess Daam2's role in neural tube development.
Main Results:
- Daam2 directly binds to Dvl2 in a Wnt-regulated manner.
- Daam2 is a cytoplasmic protein that modulates actin filament formation, thereby regulating the actin cytoskeleton.
- Loss of Daam2 in Xenopus embryos results in neural tube closure defects, indicating a role in non-canonical Wnt signaling.
- No role for Daam2 in canonical Wnt signaling was identified in mammalian cells or Xenopus.
Conclusions:
- Daam2 is identified as a component of the non-canonical Wnt pathway.
- Daam2 acts as a regulator of neural tube morphogenesis in vertebrate development.
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