Wnt–Ryk signalling mediates medial–lateral retinotectal topographic mapping
Abstract
Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity.
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During axonal guidance, another Wnt pathway via the Ryk receptor and proto-oncoprotein Src regulates repulsion of neurons.
“During axonal guidance, another Wnt pathway via the Ryk receptor and proto-oncoprotein Src regulates repulsion of neurons.104,105”
From Wnt signal transduction pathways (2008) · cites this paper as [104]
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- Authors
- Schmitt, A. M., Shi, J., Wolf, A. M., Lu, C.-C., King, L. A., & Zou, Y.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Zou, Yimin
- Venue
- Nature
- Published
- 2006-01
- Volume
- 439
- Issue
- 7072
- Pages
- 31-37
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2022247434
- Cited by
- 292
- References
- 29
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 18 · 2013: 24 · 2012: 16
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Alfred P. Sloan Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS047484)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- Wnt3, Ryk receptor, axon guidance, optic tectum, superior colliculus, retinal ganglion cell axons, Frizzled receptors, chick embryo, mice
- MeSH terms
- Animals, Axons, Brain, Chick Embryo, Genes, Dominant, Retinal Ganglion Cells, RNA, Messenger, Signal Transduction, Gene Expression Regulation, Developmental, Receptor Protein-Tyrosine Kinases, Receptors, Eph Family, Wnt Proteins, Frizzled Receptors, Mice, Wnt3 Protein
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