RYK-mediated filopodial pathfinding facilitates midgut elongation
Sha Wang1,2, James P Roy3,4, Abigail J Tomlinson2
1Department of Dermatology and Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA sha.wang149@duke.edu dgumucio@umich.edu.
Development (Cambridge, England)
|September 30, 2020
Summary
The WNT5A-RYK receptor pair guides migrating nuclei in the developing mouse midgut. This navigation is essential for cell division and rapid organ growth.
Area of Science:
- Developmental biology
- Molecular biology
- Cell biology
Background:
- Rapid elongation of the murine midgut epithelium between embryonic days 10.5 and 14.5 is driven by active cell proliferation.
- Epithelial nuclei migrate apically to divide after DNA synthesis at the basal surface.
- Post-mitotic daughter cells form filopodial protrusions for nuclear return to the basal side, guided by WNT5A secreted by mesenchymal cells.
Purpose of the Study:
- To investigate the roles of WNT5A receptors ROR2 and RYK in murine midgut epithelial pathfinding.
- To elucidate the molecular mechanisms underlying WNT5A-mediated nuclear migration and its contribution to midgut elongation.
Main Methods:
- Gene knockout studies in mice to assess the function of ROR2 and RYK.
- Phenotypic analysis of midgut development in Wnt5a, Ror2, and Ryk mutant embryos.
- Microscopy and cellular imaging to observe nuclear migration and filopodial dynamics.
Main Results:
- Epithelial ROR2 is not essential for midgut elongation.
- Loss of Ryk results in phenotypes similar to Wnt5a deficiency, including disrupted post-mitotic pathfinding and increased apoptosis.
- The WNT5A-RYK ligand-receptor interaction is identified as a crucial navigation system for filopodial pathfinding.
Conclusions:
- The WNT5A-RYK signaling pathway is critical for instructing filopodial pathfinding during midgut development.
- This pathway ensures proper nuclear migration, facilitating continuous cell cycling required for rapid midgut elongation.
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