Handling Editor: Steve Wilson
ABSTRACT
The enteric nervous system (ENS), which is derived from neural crest, is essential for gut function, and its deficiency causes severe congenital diseases. Since the capacity for ENS regeneration in mammals is limited, additional complementary models would be useful. Here, we show that the ENS in zebrafish larvae at 10-15 days postfertilization is highly regenerative. After laser ablation, the number of enteric neurons recovered to ∼50% of the control by 10 days post-ablation (dpa). Using transgenic lines in which enteric neural crest-derived cells (ENCDCs) and enteric neurons are labeled with fluorescent proteins, we live imaged the regeneration process and found covering by neurites that extended from the unablated area and entry of ENCDCs into the ablated areas by 1-3 dpa. BrdU assays suggested that ∼80% of the enteric neurons and ∼90% of the Sox10-positive ENCDCs therein at 7 dpa were generated through proliferation. Thus, ENS regeneration involves proliferation, entrance and neurogenesis of ENCDCs. This is the first report regarding the regeneration process of the zebrafish ENS. Our findings provide a basis for further in vivo research at single-cell resolution in this vertebrate model.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: M.N., K.H.; Validation: M.N.; Formal analysis: M.O., M.N., K.H.; Investigation: M.O., M.N., N.H., K.H.; Resources: K.K.; Writing - original draft: M.N.; Writing - review & editing: M.N., K.H.; Visualization: M.O., M.N., N.H., K.H.; Supervision: M.N., K.H.; Project administration: M.N., K.H.; Funding acquisition: M.N., K.K., K.H.
Funding
This work was supported by Sumitomo Foundation to M.N., Japan Society for the Promotion of Science KAKENHI 20HP8021, NBRP and NBRP/Fundamental Technologies Upgrading Program from the Japan Agency for Medical Research and Development (AMED) to K.K., and Japan Society for the Promotion of Science KAKENHI 16K06998 to K.H.
Supplementary information
Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.195339.supplemental
- Received July 22, 2020.
- Accepted December 10, 2020.
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