Ancient evolutionary origin of vertebrate enteric neurons from trunk-derived neural crest

Abstract

The enteric nervous system of jawed vertebrates arises primarily from vagal neural crest cells that migrate to the foregut and subsequently colonize and innervate the entire gastrointestinal tract. Here we examine development of the enteric nervous system in the basal jawless vertebrate the sea lamprey (Petromyzon marinus) to gain insight into its evolutionary origin. Surprisingly, we find no evidence for the existence of a vagally derived enteric neural crest population in the lamprey. Rather, labelling with the lipophilic dye DiI shows that late-migrating cells, originating from the trunk neural tube and associated with nerve fibres, differentiate into neurons within the gut wall and typhlosole. We propose that these trunk-derived neural crest cells may be homologous to Schwann cell precursors, recently shown in mammalian embryos to populate post-embryonic parasympathetic ganglia1,2, including enteric ganglia3. Our results suggest that neural-crest-derived Schwann cell precursors made an important contribution to the ancient enteric nervous system of early jawless vertebrates, a role that was largely subsumed by vagal neural crest cells in early gnathostomes.

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Figure 1: Early formation of enteric neurons in the lamprey P. marinus.
Figure 2: DiI-labelled cells in the neural tube contribute to enteric ganglia.
Figure 3: Neural tube ablation disrupts ENS development.

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Acknowledgements

We thank C. Baker, M. Piacentino, and L. Kerosuo for discussion, and M. Martik, M. Simoes-Costa, and R. Uribe for their comments on this manuscript.

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Authors

Contributions

The project was conceived by M.E.B., and analyses were designed by S.A.G. and M.E.B. Descriptive analyses of enteric neurons were performed by S.A.G. Cranial DiI labelling was performed by B.R.U., M.E.B., and S.A.G. Trunk DiI labelling was performed by B.R.U., S.A.G. and M.E.B. Surgeries were performed, imaged and analysed by S.A.G. and B.R.U. Schematics were drawn by S.A.G. The manuscript was written by M.E.B., S.A.G. and B.R.U.

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Correspondence to Marianne E. Bronner.

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The authors declare no competing financial interests.

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Extended data figures and tables

Extended Data Figure 1 Serotonin-immunoreactive cells in the gut, and DiI labelling.

a, b, 5-HT immunoreactivity in E25 (a) and E30 (b) embryos. Serotonergic neurons (yellow arrowheads) are positioned within the typhlosole, near the endodermal mucosa. A cell present in the columnar epithelium (white arrowhead) might represent an endocrine (enterochromaffin) cell. Cells positioned dorsal to the typhlosole might be neuroblasts (white arrow). c, DiI labelling results in labelled cells (yellow arrow) originating from the neural tube, migrating to the gut and typhlosole. Red, DiI; cyan, 5-HT; blue, DAPI; green, acetylated tubulin. d, e, Serotonergic (green, 5-HT; red, acetylated tubulin) neurons in a T30 embryo (d), and acetylated tubulin staining alone (e) shows the position of the vagus nerve.

Extended Data Figure 2 DiI labelling of the caudal hindbrain population shows contributions to the branchial arches.

ac, e, f, Sample time-lapse imaging of two separate DiI-labelled embryos around the hindbrain level. a, d, Initial injection at E6–E6.5 (T20). b, Final DiI localization of embryo in a, 10 days after injection (E16). c, Frontal cryosection through the branchial basket shows DiI along the branchial arches. Red, DiI; green, neurofilament-M; cyan, collagen type II. e, Final DiI localization of embryo in d 14 days after injection (E20). f, Transverse section through the lamprey branchial basket shows DiI within the dorsal root ganglia (DRG). Nt, neural tube. Red: DiI; green: neurofilament-M. g, h, Schematic depiction of individual injection sites (*) for cranial (g) and trunk (h) injections. im, Genes associated with gnathostome enteric neurons, Ret (i, l), Gfra1 (j, m), and Phox2b (k) do not appear to be co-expressed at T26 (ik) and T27 (l, m), before enteric neuron differentiation in lamprey.

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Green, S., Uy, B. & Bronner, M. Ancient evolutionary origin of vertebrate enteric neurons from trunk-derived neural crest. Nature 544, 88–91 (2017). https://doi.org/10.1038/nature21679

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