PUBLICATION
Serotonin neuromodulation directs optic nerve regeneration
- Authors
- Saied-Santiago, K., Baxter, M., Mathiaparanam, J., Granato, M.
- ID
- ZDB-PUB-250617-11
- Date
- 2025
- Source
- Development (Cambridge, England) 152: dev204334 (Journal)
- Registered Authors
- Granato, Michael
- Keywords
- Optic nerve, 5HT, Axon regeneration, Serotonin, Zebrafish
- MeSH Terms
-
- Animals
- Axons/metabolism
- Axons/physiology
- Nerve Regeneration*/drug effects
- Nerve Regeneration*/physiology
- Optic Nerve*/drug effects
- Optic Nerve*/physiology
- Optic Nerve Injuries
- Receptors, Serotonin, 5-HT1/genetics
- Receptors, Serotonin, 5-HT1/metabolism
- Retinal Ganglion Cells/metabolism
- Serotonin*/metabolism
- Signal Transduction/drug effects
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40521655 Full text @ Development
Citation
Saied-Santiago, K., Baxter, M., Mathiaparanam, J., Granato, M. (2025) Serotonin neuromodulation directs optic nerve regeneration. Development (Cambridge, England). 152:dev204334.
Abstract
Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find several serotonin type-1 receptor genes are expressed in RGC neurons during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is critical for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping