Regional cytoarchitecture of the adult and developing mouse enteric nervous system

Ryan Hamnett; Lori B Dershowitz; Vandana Sampathkumar; Ziyue Wang; Julieta Gomez-Frittelli; Vincent De Andrade; Narayanan Kasthuri; Shaul Druckmann; Julia A Kaltschmidt

doi:10.1016/j.cub.2022.08.030

Regional cytoarchitecture of the adult and developing mouse enteric nervous system

Curr Biol. 2022 Oct 24;32(20):4483-4492.e5. doi: 10.1016/j.cub.2022.08.030. Epub 2022 Sep 6.

Authors

Ryan Hamnett¹, Lori B Dershowitz¹, Vandana Sampathkumar², Ziyue Wang³, Julieta Gomez-Frittelli⁴, Vincent De Andrade⁵, Narayanan Kasthuri², Shaul Druckmann⁶, Julia A Kaltschmidt⁷

Affiliations

¹ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
² Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Biosciences Division, Argonne National Laboratory, Lemont, IL 60439, USA.
³ Department of Applied Physics, Stanford University, Stanford, CA 94305, USA; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.
⁴ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
⁵ Advanced Photon Source, Argonne National Laboratory, Lemont, IL 60439, USA.
⁶ Department of Neurobiology, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: jukalts@stanford.edu.

Abstract

The organization and cellular composition of tissues are key determinants of their biological function. In the mammalian gastrointestinal (GI) tract, the enteric nervous system (ENS) intercalates between muscular and epithelial layers of the gut wall and can control GI function independent of central nervous system (CNS) input.¹ As in the CNS, distinct regions of the GI tract are highly specialized and support diverse functions, yet the regional and spatial organization of the ENS remains poorly characterized.² Cellular arrangements,³^,⁴ circuit connectivity patterns,⁵^,⁶ and diverse cell types^7-9 are known to underpin ENS functional complexity and GI function, but enteric neurons are most typically described only as a uniform meshwork of interconnected ganglia. Here, we present a bird's eye view of the mouse ENS, describing its previously underappreciated cytoarchitecture and regional variation. We visually and computationally demonstrate that enteric neurons are organized in circumferential neuronal stripes. This organization emerges gradually during the perinatal period, with neuronal stripe formation in the small intestine (SI) preceding that in the colon. The width of neuronal stripes varies throughout the length of the GI tract, and distinct neuronal subtypes differentially populate specific regions of the GI tract, with stark contrasts between SI and colon as well as within subregions of each. This characterization provides a blueprint for future understanding of region-specific GI function and identifying ENS structural correlates of diverse GI disorders.

Keywords: development; enteric nervous system; mouse; neuronal subtypes; neurons; organization; stripes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Central Nervous System
Enteric Nervous System* / physiology
Female
Gastrointestinal Tract
Intestine, Small
Mammals
Mice
Neurons / physiology
Pregnancy

Abstract

Publication types

MeSH terms

Grants and funding