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Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3709-E3718. doi: 10.1073/pnas.1619406114. Epub 2017 Apr 18.

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis.

Author information

1
Center for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
2
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555.
3
Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, PA 17033.
4
National Tsing Hua University, Hsinchu 300, Taiwan.
5
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.
6
Center for Developmental Genetics, Department of Anesthesiology, Stony Brook University, Stony Brook, NY 11794.
7
Division of Gastroenterology, Stanford University School of Medicine, Stanford, CA 94305.
8
Department of Biomedical Engineering, Duke University, Durham, NC 27708.
9
School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853.
10
Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
11
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
12
Department of Dermatology, Center for Sensory Biology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
13
Howard Hughes Medical Institute, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
14
Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
15
Institute for Cellular Engineering, Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
16
Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
17
Department of Laboratories, Seattle Children's Hospital, Seattle, WA 98105.
18
Center for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; ppasric1@jhmi.edu.

Abstract

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

KEYWORDS:

Nestin; adult neurogenesis; enteric neural precursor cells; enteric neurons; neuronal apoptosis

PMID:
28420791
PMCID:
PMC5422809
DOI:
10.1073/pnas.1619406114
[Indexed for MEDLINE]
Free PMC Article

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