Lineage-dependent Spatial and Functional Organization of the Mammalian Enteric Nervous System

Lasrado R., Boesmans W., Kleinjung J., Pin C., Bell D., Bhaw L., McCallum S., Zong H., Luo L., Clevers H., Vanden Berghe P., Pachnis V.. (2017)

Science, 356, 6339 722-726

The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here, we show that the amorphous neuroglia networks of mouse ENS are composed of overlapping clonal units founded by post-migratory neural crest-derived progenitors. The spatial configuration of ENS clones depends on proliferation-driven local interactions of ENS progenitors with lineally unrelated neuroectodermal cells, the ordered colonization of the serosa-mucosa axis by clonal descendants and gut expansion. Single cell transcriptomics and mutagenesis analysis delineated dynamic molecular states of ENS progenitors and identified RET as a regulator of neurogenic commitment. Clonally related enteric neurons exhibit synchronous activity in response to network stimulation. Thus, lineage relationships underpin the organization of the peripheral nervous system.

Science, 356, 6339 722-726

View Publication