Neuronal Development and Onset of Electrical Activity in the Human Enteric Nervous System.
Calcium Signaling
Colon
/ embryology
Electric Stimulation
Enteric Nervous System
/ drug effects
Evoked Potentials
/ drug effects
Female
Gene Expression Regulation, Developmental
Gestational Age
Humans
Nerve Net
/ drug effects
Neurogenesis
/ drug effects
Neurons
/ drug effects
Neurotransmitter Agents
/ pharmacology
Phenotype
Pregnancy
Pregnancy Trimester, Second
Synaptic Transmission
Embryology
Fetal
Fetus
Intestine
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
29
04
2018
revised:
07
12
2018
accepted:
24
12
2018
pubmed:
6
1
2019
medline:
6
5
2019
entrez:
6
1
2019
Statut:
ppublish
Résumé
The enteric nervous system (ENS) is the largest branch of the peripheral nervous system, comprising complex networks of neurons and glia, which are present throughout the gastrointestinal tract. Although development of a fully functional ENS is required for gastrointestinal motility, little is known about the ontogeny of ENS function in humans. We studied the development of neuronal subtypes and the emergence of evoked electrical activity in the developing human ENS. Human fetal gut samples (obtained via the MRC-Wellcome Trust Human Developmental Biology Resource-UK) were characterized by immunohistochemistry, calcium imaging, RNA sequencing, and quantitative real-time polymerase chain reaction analyses. Human fetal colon samples have dense neuronal networks at the level of the myenteric plexus by embryonic week (EW) 12, with expression of excitatory neurotransmitter and synaptic markers. By contrast, markers of inhibitory neurotransmitters were not observed until EW14. Electrical train stimulation of internodal strands did not evoke activity in the ENS of EW12 or EW14 tissues. However, compound calcium activation was observed at EW16, which was blocked by the addition of 1 μmol/L tetrodotoxin. Expression analyses showed that this activity was coincident with increases in expression of genes encoding proteins involved in neurotransmission and action potential generation. In analyses of human fetal intestinal samples, we followed development of neuronal diversity, electrical excitability, and network formation in the ENS. These processes are required to establish the functional enteric circuitry. Further studies could increase our understanding of the pathogenesis of a range of congenital enteric neuropathies.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
The enteric nervous system (ENS) is the largest branch of the peripheral nervous system, comprising complex networks of neurons and glia, which are present throughout the gastrointestinal tract. Although development of a fully functional ENS is required for gastrointestinal motility, little is known about the ontogeny of ENS function in humans. We studied the development of neuronal subtypes and the emergence of evoked electrical activity in the developing human ENS.
METHODS
METHODS
Human fetal gut samples (obtained via the MRC-Wellcome Trust Human Developmental Biology Resource-UK) were characterized by immunohistochemistry, calcium imaging, RNA sequencing, and quantitative real-time polymerase chain reaction analyses.
RESULTS
RESULTS
Human fetal colon samples have dense neuronal networks at the level of the myenteric plexus by embryonic week (EW) 12, with expression of excitatory neurotransmitter and synaptic markers. By contrast, markers of inhibitory neurotransmitters were not observed until EW14. Electrical train stimulation of internodal strands did not evoke activity in the ENS of EW12 or EW14 tissues. However, compound calcium activation was observed at EW16, which was blocked by the addition of 1 μmol/L tetrodotoxin. Expression analyses showed that this activity was coincident with increases in expression of genes encoding proteins involved in neurotransmission and action potential generation.
CONCLUSIONS
CONCLUSIONS
In analyses of human fetal intestinal samples, we followed development of neuronal diversity, electrical excitability, and network formation in the ENS. These processes are required to establish the functional enteric circuitry. Further studies could increase our understanding of the pathogenesis of a range of congenital enteric neuropathies.
Identifiants
pubmed: 30610864
pii: S0016-5085(18)35435-0
doi: 10.1053/j.gastro.2018.12.020
pii:
doi:
Substances chimiques
Neurotransmitter Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1483-1495.e6Subventions
Organisme : Medical Research Council
ID : G0800973
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R006237/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 099175/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : 099175/Z/12/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.