Unbiased characterization of the larval zebrafish enteric nervous system at a single cell transcriptomic level

• Type of Material: Article
• Authors: Laura E Kuil, Erasmus University; Naomi J.M Kakiailatu, Erasmus University; Jonathan D Windster, Erasmus University; Eric Bindels, Erasmus MC, Rotterdam; Joke T.M Zink, Erasmus MC, Rotterdam; Gaby van der Zee, Erasmus University; Robert M.W Hofstra, Erasmus University; Iain T Shepherd, Emory University; Veerle Melotte, Erasmus University; Maria M. Alves, Erasmus University
• Language: English
• Date: 2023-07-21
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.isci.2023.107070
• Title of Journal or Parent Work: iScience
• Volume: 26
• Issue: 7
• Keywords: Neuroscience; Developmental neuroscience; enteric nervous system(ENS); immune regulation; Transcriptomics
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology; Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Public Health

Abstract

The enteric nervous system (ENS) regulates many gastrointestinal functions including peristalsis, immune regulation and uptake of nutrients. Defects in the ENS can lead to severe enteric neuropathies such as Hirschsprung disease (HSCR). Zebrafish have proven to be fruitful in the identification of genes involved in ENS development and HSCR pathogenesis. However, composition and specification of enteric neurons and glial subtypes at larval stages, remains mainly unexplored. Here, we performed single cell RNA sequencing of zebrafish ENS at 5 days post-fertilization. We identified vagal neural crest progenitors, Schwann cell precursors, and four clusters of differentiated neurons. In addition, a previously unrecognized elavl3+/phox2bb-population of neurons and cx43+/phox2bb-enteric glia was found. Pseudotime analysis supported binary neurogenic branching of ENS differentiation, driven by a notch-responsive state. Taken together, we provide new insights on ENS development and specification, proving that the zebrafish is a valuable model for the study of congenital enteric neuropathies.