Morphological evidence suggestive of a hierarchical mode of glial cell diversification and intrinsic developmental plasticity within the murine enteric nervous system.

Enteric glial cells represent a highly heterogeneous cell population residing both within and outside the ganglia and inter-ganglionic fiber bundles that form the core networks of the enteric nervous system (ENS). Despite the availability of several relevant single-cell transcriptomic datasets, the classification of enteric glia in various subtypes is still mainly based on their particular location and associated morphological attributes. We recently reported that these "topo-morphological" enteric glia subtypes gradually appear during early postnatal development in healthy wildtype mice, under the influence of structural tissue changes that occur during this period. This process is also influenced by the source of ENS progenitors, with notable biased contributions by Schwann cell precursors (SCPs). This prior work further suggested the existence of a hierarchical program of spatiotemporal differentiation, whereby intra-network enteric glia (i.e., within ganglia and fiber bundles) of the myenteric plexus sequentially give rise to nearby extra-network enteric glia as well as to more distant intra- and extra-network enteric glia of the submucosal plexus. To learn more about enteric glia diversification, we reasoned that the