2. Academic Validation
  3. Tachykinin signaling defines distinct populations of glia in the enteric nervous system

Tachykinin signaling defines distinct populations of glia in the enteric nervous system

  • Neuron. 2026 Jan 8:S0896-6273(25)00927-4. doi: 10.1016/j.neuron.2025.11.030.
Anoohya N Muppirala 1,  Perry E Mitchell 1,  Elise Courtney 1,  Sushmita Debnath 2,  Lia R D'Alessandro 1,  Neha Mani 1,  Maryam Dadabhoy 1,  Ariel Robinson 1,  Cristian Díaz-Muñoz 3,  Maria D Paraskevopoulou 4,  Mauro D'Amato 5,  Thomas W Gould 2,  Meenakshi Rao 6
Affiliations

Affiliations

  • 1 Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • 2 Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, NV, USA.
  • 3 Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.
  • 4 Takeda Development Center Americas, Inc., Cambridge, MA, USA.
  • 5 Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; Ikerbasque, Basque Science Foundation, Bilbao, Spain; Department of Medicine and Surgery, LUM University, Casamassima, Italy.
  • 6 Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
PMID: 41512855 DOI: 10.1016/j.neuron.2025.11.030
Abstract

One of the largest glial populations outside the brain is in the gut. These enteric glia are involved in many functions, from intestinal peristalsis to immunity, yet it is unclear whether subtypes exist with distinct roles in homeostasis. Comparing glia from divergent microenvironments in the mouse intestine, we found that mucosal glia most resembled microglia, while muscularis glia resembled satellite glia. Tacr3, encoding the receptor for neuropeptide neurokinin B (NKB), was enriched within muscularis glia associated with neuronal soma and was undetectable in extraintestinal glia. Genetic or pharmacological manipulation of NKB-TACR3 signaling disrupted the establishment of enteric glial populations during postnatal development and dynamically modulated intestinal motor behaviors in adult mice. Collectively, we delineate spatially, transcriptionally, and functionally distinct populations of enteric glia; identify one as an unanticipated target of TACR3 antagonists in clinical use; and establish this pathway as necessary for enteric glial diversification and function.

Keywords

ENS; NK3R; TAC2; TACR3; enteric glia; fezolinetant; intestinal motility; neural crest; neuropeptide; peripheral nervous system.

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