Kulkarni, S., Micci, M. A., Leser, J., Shin, C., Tang, S. C., Fu, Y. Y., Liu, L., Li, Q., Saha, M., Li, C., Enikolopov, G., Becker, L., Rakhilin, N., Anderson, M., Shen, X., Dong, X., Butte, M. J., Song, H., Southard-Smith, E. M., Kapur, R. P., Bogunovic, M., Pasricha, P. J. (May 2017) Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc Natl Acad Sci U S A, 114 (18). E3709-E3718. ISSN 0027-8424
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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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Nestin adult neurogenesis enteric neural precursor cells enteric neurons neuronal apoptosis |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neurogenesis |
| CSHL Authors: | |
| Communities: | CSHL labs > Enikopolov lab |
| Depositing User: | Matt Covey |
| Date: | 2 May 2017 |
| Date Deposited: | 28 Apr 2017 15:46 |
| Last Modified: | 08 Nov 2017 19:06 |
| PMCID: | PMC5422809 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/34655 |
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