Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Biosciences Division, Argonne National Laboratory, Lemont, IL 60439, USA.
Curr Biol. 2022 Oct 24;32(20):4483-4492.e5. doi: 10.1016/j.cub.2022.08.030. Epub 2022 Sep 6.
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. 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.
组织和细胞组成是决定组织生物学功能的关键因素。在哺乳动物胃肠道（GI）中，肠神经系统（ENS）位于肠道壁的肌肉层和上皮层之间，可以独立于中枢神经系统（CNS）输入来控制 GI 功能。与 CNS 一样，胃肠道的不同区域高度专业化，支持多种功能，但 ENS 的区域和空间组织仍未得到充分描述。细胞排列、电路连接模式和多种细胞类型是 ENS 功能复杂性和 GI 功能的基础，但肠神经元通常仅被描述为相互连接的神经节的统一网格。在这里，我们提供了一个对小鼠 ENS 的鸟瞰图，描述了其以前未被充分认识的细胞结构和区域变化。我们通过视觉和计算方法证明，肠神经元以环状神经元条纹的形式组织。这种组织在围产期逐渐形成，小肠（SI）中的神经元条纹形成先于结肠中的神经元条纹形成。神经元条纹的宽度在整个 GI 道长度上变化，不同的神经元亚型在 GI 道的特定区域中不同程度地存在，SI 和结肠之间以及每个区域的内部都存在明显的对比。这种特征为未来理解特定区域的 GI 功能以及确定不同 GI 疾病的 ENS 结构相关性提供了蓝图。
