De novo enteric neurogenesis in post-embryonic zebrafish from Schwann cell precursors rather than resident cell types

Abstract

The enteric nervous system (ENS) is essential for normal gastrointestinal function. While the embryonic origin of enteric neurons from the neural crest is well-established, conflicting evidence exists regarding postnatal enteric neurogenesis. Here, we address this by examining the origin of de novo neurogenesis in the post-embryonic zebrafish ENS. While new neurons are added during growth and after injury, the larval intestine appears to lack resident neurogenic precursors or classical glia marked by Sox10, PLP1a, GFAP or S100. Rather, lineage tracing with lipophilic dye or inducible Sox10-Cre suggest that post-embryonic enteric neurons arise from trunk neural crest-derived Schwann cell precursors that migrate from the spinal cord into the intestine. Furthermore, the 5-HT4 receptor agonist prucalopride increases enteric neurogenesis in normal development and after injury. Taken together, the results suggest that despite the lack of resident progenitors in the gut, post-embryonic enteric neurogenesis occurs via gut-extrinsic Schwann cell precursors during both development and injury, and is promoted by serotonin agonists. The absence of classical glia in the ENS further suggests that neural crest-derived enteric glia may have evolved after the teleost lineage.