Regional cytoarchitecture of the adult and developing mouse enteric nervous system

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. 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, circuit connectivity patterns, and diverse cell types 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.

组织的结构与细胞组成是决定其生物学功能的核心决定因素。在哺乳动物胃肠道（gastrointestinal，GI）中，肠神经系统（enteric nervous system，ENS）嵌合于肠壁的肌层与上皮层之间，可不依赖中枢神经系统（central nervous system，CNS）的输入信号调控胃肠道功能。与中枢神经系统类似，胃肠道的不同区域具有高度特化的结构并承担多样化的生理功能，但目前肠神经系统的区域与空间组织结构仍未得到充分解析[2]。
已知细胞排布方式、环路连接模式与多种细胞类型共同支撑肠神经系统的功能复杂性与胃肠道生理功能，但目前对肠神经元的主流认知仍仅停留在其为相互连接的神经节构成的均匀网状结构这一层面。
本研究首次全景呈现小鼠肠神经系统的结构全貌，揭示了其此前未被充分认知的细胞构筑与区域差异。我们通过视觉成像与计算分析证实，肠神经元以环形神经元条带的形式有序排布。这种组织结构在围产期逐步形成，且小肠（small intestine，SI）的神经元条带形成进程早于结肠。
神经元条带的宽度随胃肠道走行发生动态变化，不同神经元亚型在胃肠道的特定区域呈现差异化分布，小肠与结肠之间以及二者各自的亚区域之间均存在显著差异。
本研究的表征工作为未来解析区域特异性胃肠道功能、探究多种胃肠道疾病的肠神经系统结构关联提供了重要参考蓝图。