ABSTRACT
The enteric nervous system is essential for normal gastrointestinal function, but evidence regarding postnatal enteric neurogenesis is conflicting. Using zebrafish as a model, we explored the origin of enteric neurons that arise in post-embryonic life in normal development and injury, and tested effects of the 5-HT4 receptor agonist, prucalopride.
To assess enteric neurogenesis, all enteric neurons were photoconverted prior to time-lapse imaging to detect emergence of new neurons. Injury was modeled by two-photon laser ablation of enteric neurons. Lineage tracing was performed with neural tube injections of lipophilic dye and with an inducible Sox10-Cre line. Lastly, we tested prucalopride’s effect on post-embryonic enteric neurogenesis.
The post-embryonic zebrafish intestine appears to lack resident neurogenic precursors and enteric glia. However, enteric neurogenesis persists post-embryonically during development and after injury. New enteric neurons arise from trunk neural crest-derived Schwann cell precursors. Prucalopride increases enteric neurogenesis in normal development and after injury if exposure occurs prior to injury.
Enteric neurogenesis persists in the post-embryonic period in both normal development and injury, appears to arise from gut-extrinsic Schwann cell precursors, and is promoted by prucalopride.
SUMMARY STATEMENT Trunk crest-derived enteric neurogenesis is poorly understood. We find post-embryonic zebrafish lack resident neuronal precursors yet enteric neurogenesis from trunk crest-derived precursors occurs in development, injury, and is promoted by prucalopride.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
* Grant support: NIH R35NS111564, NIH R01NS108500, UCLA Specialty Training and Advanced Research Program, UCLA Division of Digestive Diseases Seed Grant
WN El-Nachef: no conflicts to disclose
ME Bronner: no conflicts to disclose
Writing assistance: N/A
Abbreviations
- ENS
- enteric nervous system
- SCP
- Schwann cell precursor
- ISH
- in situ hybridization
- IHC
- immunohistochemistry
- dpf
- days post fertilization
- hpf
- hours post fertilization
- 5HT4R
- 5-HT4 receptor