The transcriptomes, connections and development of submucosal neuron classes in the mouse small intestine

作者：Wei Li, Khomgrit Morarach, Ziwei Liu, Sanghita Banerjee, Yanan Chen, Ashley L. Harb, Joel M. Kosareff, Charles Hall, Fernando Martínez López, Elham Jalalvand, Suad Mohamed, Anastassia Mikhailova, David R. Linden, Ulrika Marklund · 发表于：Nature Neuroscience · 年份：2025 · DOI：10.1038/s41593-025-01962-x · 被引用次数：18 · 研究领域：Congenital gastrointestinal and neural anomalies、Congenital heart defects research、Gastrointestinal motility and disorders

The enteric submucosal plexus regulates essential digestive functions, yet its neuronal composition remains incompletely understood. We identified two putative secretomotor neuron classes and a previously unrecognized submucosal intrinsic primary afferent neuron class through single-cell RNA sequencing in the mouse small intestine. Using viral-mediated labeling of each class, we uncovered their morphologies and neural projections in the submucosa-mucosa context, finding connections among all classes and an unexpected close association with enterochromaffin cells. Further transcriptome analysis at the postnatal stage and lineage tracing revealed that neuron identities in the submucosal plexus emerge through an initial binary fate split at neurogenesis, followed by phenotypic diversification, akin to the developmental process of the myenteric plexus. We propose a unified developmental framework for neuronal diversification across the gut wall. Our study offers comprehensive molecular, developmental and morphological insights into submucosal neurons, opening new avenues for exploring physiological functions, circuit dynamics and formation of the submucosal plexus.