1. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system.
- Author
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Lasrado R, Boesmans W, Kleinjung J, Pin C, Bell D, Bhaw L, McCallum S, Zong H, Luo L, Clevers H, Vanden Berghe P, and Pachnis V
- Subjects
- Animals, Cell Proliferation, Clone Cells cytology, Enteric Nervous System metabolism, Intestinal Mucosa cytology, Mice, Mosaicism, Mutagenesis, Neural Crest cytology, Neurogenesis, Neuroglia physiology, Neurons cytology, Sequence Analysis, RNA, Signal Transduction, Single-Cell Analysis, Stem Cells cytology, Transcriptome, Cell Lineage genetics, Enteric Nervous System cytology
- Abstract
The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here we show that the amorphous neuroglia networks of the mouse ENS are composed of overlapping clonal units founded by postmigratory 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., (Copyright © 2017, American Association for the Advancement of Science.)
- Published
- 2017
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