RT Journal Article
SR Electronic
T1 Neural crest-derived neurons are replaced by a newly identified mesodermal lineage in the post-natal and aging enteric nervous system
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.25.262832
DO 10.1101/2020.08.25.262832
A1 Subhash Kulkarni
A1 Monalee Saha
A1 Laren Becker
A1 Zhuolun Wang
A1 Guosheng Liu
A1 Jenna Leser
A1 Mithra Kumar
A1 Shriya Bakhshi
A1 Matthew Anderson
A1 Mark Lewandoski
A1 Jared Slosberg
A1 Sushma Nagaraj
A1 Elizabeth Vincent
A1 Loyal A. Goff
A1 Pankaj Jay Pasricha
YR 2020
UL http://biorxiv.org/content/early/2020/08/25/2020.08.25.262832.abstract
AB The enteric nervous system (ENS), a collection of neurons contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the embryonic neural crest and remains largely unchanged thereafter. Here, we show that the composition of maturing ENS changes with time, with a decline in neural-crest derived neurons and their replacement by mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.Competing Interest StatementThe authors have declared no competing interest.