Organ-specific sympathetic innervation defines visceral functions
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1.
California Institute of Technology
Abstract
The autonomic nervous system orchestrates the functions of the brain and body through the sympathetic and parasympathetic pathways1. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac–superior mesenteric ganglia (CG–SMG). Of note, individual CG–SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG–SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations.
Copyright and License
© 2024, The Author(s), under exclusive licence to Springer Nature Limited
Acknowledgement
We thank the members of the Oka laboratory; Y. Zhang and T. Ichiki for helpful discussion and comments; J. Hauser, M. Oka and A. Tufenkjian for maintaining and genotyping mouse lines; Y. Zhang for helping with data analysis; Q. Liang and Y. Chen for providing the SHOX2–Cre line; B. Zhang and K. Frieda for help on seqFISH experiments; J. Linton, F. Horns and M. Elowitz for sharing the cell sorter; D. Anderson and the Single-Cell Profiling and Engineering Center for instrumental support with scRNA-seq experiments; and W. Han and I. De Araujo for advice on surgical techniques. This work was supported by Startup funds from the President and Provost of California Institute of Technology and the Biology and Biological Engineering Division of California Institute of Technology. Y.O. is also supported by the New York Stem Cell Foundation, the US National Institutes of Health (R01NS109997 and R01NS123918), the Alfred P. Sloan Foundation, the Edward Mallinckrodt Foundation and the Heritage Medical Research Institute.
Contributions
T.W. and Y.O. conceived the research programme and designed the experiments. T.W. performed the transcriptomic, genetic, behavioural and anatomical experiments and analysed the data. B.T. performed the electrophysiological and behavioural experiments. D.R.Y. and W.G. designed and fabricated a microfluidic device for bile measurement. T.W. and Y.O. wrote the paper. Y.O. supervised the work.
Data Availability
scRNA-seq data from CG–SMG cells are available at the Gene Expression Omnibus under the accession number GSE278457. The organ innervation and seqFISH data have been deposited at Zenodo (#13306861 and #13883320)59,60. Source data are provided with this paper.
Code Availability
The code used in this paper is available at https://github.com/YTwTJ/Organ-Specific-Sympathetic-Innervation-Defines-Visceral-Functions.
Supplemental Material
- Supplementary Information: Supplementary Fig. 1 and Supplementary Tables 1 and 2
- Supplementary Data for Supplementary Fig. 1: Source data for Supplementary Fig. 1
Files
Additional details
- Accepted
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2024-10-22Accepted
- Available
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2024-11-27Published online
- Caltech groups
- Division of Biology and Biological Engineering
- Publication Status
- Published