Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

ENTERIC NERVOUS SYSTEM

Revealing the complexity of the gut’s brain

Nature Neuroscience volume 24, pages 1–2 (2021)Cite this article

Subjects

A new study proposes an exciting new model of neuronal diversification in the developing enteric nervous system (ENS) and establishes a detailed molecular taxonomy for enteric neurons. Their findings open new horizons for ENS research and for developing cell-based therapies for ENS disorders.

Previous work on the molecular basis of neuronal diversity in the ENS has been hampered by the technical challenge of isolating viable ENS neurons from their ganglia. The authors used an improved protocol for cell dissociation to isolate many more ENS neurons than in their previous study7. They also used a new Cre-line that broadly labels enteric neurons and allows for the efficient enrichment of ENS neurons. With this improved approach, they provided a comprehensive classification of twelve enteric neurons classes (ENCs) based on single-cell RNA-seq of isolated neurons from the myenteric plexus in juvenile mice. Using extensive co-staining with established markers, they were able to relate the twelve neuron classes to previously discovered molecular characteristics of functional enteric neuron types, thus classifying the ENCs into excitatory and inhibitory motor neurons, interneurons, and intrinsic primary afferent neurons (Fig. 1). Importantly, this analysis showed that each ENC was distinguishable by its expression of transcription factor genes and other gene families in unique combinations (for example, adhesion molecules and modulators of synaptic plasticity). These findings put forward novel sets of molecular players that can now be tested for their role in regulating stem cell maintenance, neuronal differentiation and specification, and circuit formation in the ENS. This work generates a multitude of new research questions and directions, from the molecular control of neuronal diversification to connectivity, all poorly understood areas of ENS development and function.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Twelve unique ENCs arise from a binary fate split during development with subsequent diversification of postmitotic neuronal populations.

References

  1. Furness, J.B. The Enteric Nervous System (Blackwell Publishing, 2006).

  2. Ganz, J., Melancon, E. & Eisen, J. S. Methods Cell Biol. 134, 139–164 (2016).

    Article  CAS  Google Scholar 

  3. Neunlist, M. et al. Nat. Rev. Gastroenterol. Hepatol. 10, 90–100 (2013).

    Article  CAS  Google Scholar 

  4. Ganz, J. Dev. Dyn. 247, 268–278 (2018).

    Article  Google Scholar 

  5. Rao, M. & Gershon, M. D. Nat. Rev. Neurosci. 19, 552–565 (2018).

    Article  CAS  Google Scholar 

  6. Morarach, K. et al. Nat. Neurosci. https://doi.org/10.1038/s41593-020-00736-x (2020).

  7. Zeisel, A. et al. Cell 174, 999–1014.e22 (2018).

    Article  CAS  Google Scholar 

  8. Holguera, I. & Desplan, C. Science 362, 176–180 (2018).

    Article  CAS  Google Scholar 

  9. Lasrado, R. et al. Science 356, 722–726 (2017).

    Article  CAS  Google Scholar 

  10. Drokhlyansky, E. et al. Cell 182, 1606–1622.e23 (2020).

    Article  CAS  Google Scholar 

  11. May-Zhang, A.A. et al. Gastroenterology https://doi.org/10.1053/j.gastro.2020.09.032 (2020).

  12. Brosens, E. et al. Dev. Biol. 417, 198–208 (2016).

    Article  CAS  Google Scholar 

  13. Heuckeroth, R. O. Nat. Rev. Gastroenterol. Hepatol. 15, 152–167 (2018).

    Article  Google Scholar 

  14. Rao, M. & Gershon, M. D. Nat. Rev. Gastroenterol. Hepatol. 13, 517–528 (2016).

    Article  CAS  Google Scholar 

  15. Burns, A. J. et al. Dev. Biol. 417, 229–251 (2016).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Integrative Biology, Michigan State University, East Lansing, MI, USA

    Julia Ganz

Authors
  1. Julia Ganz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julia Ganz.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ganz, J. Revealing the complexity of the gut’s brain. Nat Neurosci 24, 1–2 (2021). https://doi.org/10.1038/s41593-020-00769-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-020-00769-2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing