ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 38 citations in OpenAlex.
- Modeling human retinal ganglion cell axonal outgrowth, development, and pathology using pluripotent stem cell-based microfluidic platforms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Development of the Binocular Circuit.Annual review of neuroscience · 2024Review
- KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors.Nature communications · 2023Article
- Signaling - transcription interactions in mouse retinal ganglion cells early axon pathfinding -a literature review.Frontiers in ophthalmology · 2023Review
- Article
- New insights into the molecular mechanisms of axon guidance receptor regulation and signaling.Current topics in developmental biology · 2021Review
- Molecular mechanisms regulating axon responsiveness at the midline.Developmental biology · 2020Article
- The transcription factorDisease models & mechanisms · 2020Article
- Sfrp1 deficiency makes retinal photoreceptors prone to degeneration.Scientific reports · 2020Article
- Revisiting the role of Dcc in visual system development with a novel eye clearing method.eLife · 2020Article
- The Horizontal Raphe of the Human Retina and its Watershed Zones.Vision (Basel, Switzerland) · 2019Review
- Elevated levels of Secreted-Frizzled-Related-Protein 1 contribute to Alzheimer's disease pathogenesis.Nature neuroscience · 2019Article
- Proteolytic cleavage of host proteins by the Group IV viral proteases of Venezuelan equine encephalitis virus and Zika virus.Antiviral research · 2019Article
- Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.Cell death & disease · 2018Article
- Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- DSCAM promotes axon fasciculation and growth in the developing optic pathway.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Where does axon guidance lead us?F1000Research · 2017Review
- Proteases at work: cues for understanding neural development and degeneration.Frontiers in molecular neuroscience · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retina ganglion cell (RGC) axons grow along a stereotyped pathway undergoing coordinated rounds of fasciculation and defasciculation, which are critical to establishing proper eye-brain connections. How this coordination is achieved is poorly understood, but shedding of guidance cues by metalloproteinases is emerging as a relevant mechanism. Secreted Frizzled Related Proteins (Sfrps) are multifunctional proteins, which, among others, reorient RGC growth cones by regulating intracellular second messengers, and interact with Tolloid and ADAM metalloproteinases, thereby repressing their activity. Here, we show that the combination of these two functions well explain the axon guidance phenotype observed in Sfrp1 and Sfrp2 single and compound mouse mutant embryos, in which RGC axons make subtle but significant mistakes during their intraretinal growth and inappropriately defasciculate along their pathway. The distribution of Sfrp1 and Sfrp2 in the eye is consistent with the idea that Sfrp1/2 normally constrain axon growth into the fiber layer and the optic disc. Disheveled axon growth instead seems linked to Sfrp-mediated modulation of metalloproteinase activity. Indeed, retinal explants from embryos with different Sfrp-null alleles or explants overexpressing ADAM10 extend axons with a disheveled appearance, which is reverted by the addition of Sfrp1 or an ADAM10-specific inhibitor. This mode of growth is associated with an abnormal proteolytic processing of L1 and N-cadherin, two ADAM10 substrates previously implicated in axon guidance. We thus propose that Sfrps contribute to coordinate visual axon growth with a dual mechanism: by directly signaling at the growth cone and by regulating the processing of other relevant cues.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.