Neurogenesis in the insect enteric nervous system: generation of premigratory neurons from an epithelial placode

The enteric plexus (EP) is a major division of the enteric nervous system (ENS) in the moth Manduca sexta and contains a dispersed population of about 360 bipolar neurons, the EP cells. Previously we showed that embryonic EP cells achieve their mature distributions by extensive migration along the gut surface and then display position-specific phenotypes. We now demonstrate that the entire EP cell population is generated from an ectodermal placode that invaginates from the embryonic foregut. Individual EP cells become postmitotic just as they leave the epithelium, but their terminal differentiation is subsequently delayed until after their migratory dispersal. Clonal analysis by injection of lineage-tracing dyes has shown that the EP cell population is derived from a large number of placodal cells, each of which contributes a limited number of neurons to the ENS. Placodally derived clones produce neurons exclusively, while clones arising from cells adjacent to the placode are incorporated into the gut epithelium. These results indicate that neurogenesis in the insect ENS involves a developmental strategy that is distinct from that seen in the insect CNS and which resembles the generation of certain cell classes in the vertebrate nervous system.

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Changes in Immunoreactivity of Sensory Substances within the Enteric Nervous System of the Porcine Stomach during Experimentally Induced Diabetes

Journal of Diabetes Research ◽

10.1155/2018/4735659 ◽

2018 ◽

Vol 2018 ◽

pp. 1-18 ◽

Cited By ~ 9

Author(s):

Michał Bulc ◽

Katarzyna Palus ◽

Jarosław Całka ◽

Łukasz Zielonka

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Porcine Model ◽

Enteric Neurons ◽

Submucosal Plexus ◽

Chemical Coding ◽

Chemically Induced ◽

Calcitonin Gene ◽

Enteric Plexus ◽

Clear Increase

One of the most frequently reported disorders associated with diabetes is gastrointestinal (GI) disturbance. Although pathogenesis of these complications is multifactorial, the complicity of the enteric nervous system (ENS) in this respect has significant importance. Therefore, this paper analysed changes in substance P- (SP-), calcitonin gene-related peptide- (CGRP-), and leu5-enkephalin- (L-ENK-) like immunoreactivity (LI) in enteric stomach neurons caused by chemically induced diabetes in a porcine model. Using double immunofluorescent labelling, it was found that acute hyperglycaemia led to significant changes in the chemical coding of stomach enteric neurons. Generally, the response to artificially inducted diabetes depended on the “kind” of enteric plexus as well as the stomach region studied. A clear increase in the percentage of neurons immunoreactive to SP and CGRP was visible in the myenteric plexus (MP) in the antrum, corpus, and pylorus as well as in the submucosal plexus (SmP) in the corpus. For L-ENK, an increase in the number of L-ENK-LI neurons was observed in the MP of the antrum and SmP in the corpus, while in the MP of the corpus and pylorus, a decrease in the percentage of L-ENK-LI neurons was noted.

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Cell lineage tracing in the developing enteric nervous system: superstars revealed by experiment and simulation

Journal of The Royal Society Interface ◽

10.1098/rsif.2013.0815 ◽

2014 ◽

Vol 11 (93) ◽

pp. 20130815 ◽

Cited By ~ 31

Author(s):

Bevan L. Cheeseman ◽

Dongcheng Zhang ◽

Benjamin J. Binder ◽

Donald F. Newgreen ◽

Kerry A. Landman

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Cell Fate ◽

Cell Lineage ◽

Population Expansion ◽

Population Level ◽

Lineage Tracing ◽

Model Parameters ◽

Agent Based ◽

Proliferation And Differentiation

Cell lineage tracing is a powerful tool for understanding how proliferation and differentiation of individual cells contribute to population behaviour. In the developing enteric nervous system (ENS), enteric neural crest (ENC) cells move and undergo massive population expansion by cell division within self-growing mesenchymal tissue. We show that single ENC cells labelled to follow clonality in the intestine reveal extraordinary and unpredictable variation in number and position of descendant cells, even though ENS development is highly predictable at the population level. We use an agent-based model to simulate ENC colonization and obtain agent lineage tracing data, which we analyse using econometric data analysis tools. In all realizations, a small proportion of identical initial agents accounts for a substantial proportion of the total final agent population. We term these individuals superstars. Their existence is consistent across individual realizations and is robust to changes in model parameters. This inequality of outcome is amplified at elevated proliferation rate. The experiments and model suggest that stochastic competition for resources is an important concept when understanding biological processes which feature high levels of cell proliferation. The results have implications for cell-fate processes in the ENS.

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Origins of the insect enteric nervous system: differentiation of the enteric ganglia from a neurogenic epithelium

Development ◽

10.1242/dev.113.4.1115 ◽

1991 ◽

Vol 113 (4) ◽

pp. 1115-1132 ◽

Cited By ~ 2

Author(s):

P.F. Copenhaver ◽

P.H. Taghert

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Enteric Nervous System ◽

Neural Progenitors ◽

Developmental Sequence ◽

Cortical Layers ◽

Enteric Ganglia ◽

Enteric Plexus ◽

Insect Central Nervous System ◽

System Differentiation

The enteric nervous system (ENS) of the moth Manduca sexta is organized into two distinct cellular domains: an anterior domain that includes several small ganglia on the surface of the foregut, and a more posterior domain consisting of a branching nerve plexus (the enteric plexus) that spans the foregut-midgut boundary. Previously, we showed that the neurons of the posterior domain, the enteric plexus, are generated from a large placode that invaginates from the caudal lip of the foregut; subsequently, the cells become distributed throughout the enteric plexus by a sequence of active migration. We now demonstrate that the neurons of the anterior domain, the cells of the enteric ganglia, arise via a distinct developmental sequence. Shortly after the foregut has begun to form, three neurogenic zones differentiate within the foregut epithelium and give rise to chains of cells that emerge onto the foregut surface. The three zones are not sites of active mitosis, as indicated by the absence of labelling with a thymidine analogue and by clonal analyses using intracellularly injected dyes. Rather, the zones serve as loci through which epithelial cells are recruited into a sequence of delamination and neuronal differentiation. As they emerge from the epithelium, the cells briefly become mitotically active, each cell dividing once or twice. In this manner, they resemble the midline precursor class of neural progenitors in the insect central nervous system more than neuroblast stem cells. The progeny of these zone-derived precursors then gradually coalesce into the ganglia and nerves of the anterior ENS. Although this reorganization results in some variability in the precise configuration of neurons within the ganglia, the overall morphology of the ganglia is highly stereotyped, consisting of cortical layers of cells that surround a ventral neuropil. In addition, a number of the neurons within the frontal and hypocerebral ganglia express identifiable phenotypes in a manner that is similar to many cells of the insect central nervous system. These observations indicate that the differentiation of the enteric ganglia in Manduca involves an unusual combination of features seen during the formation of other regions of the nervous system and, as such, constitutes a distinct program of neurogenesis.

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515a DCLK1 Labels a Multipotent and Residual Neural Crest-Derived Stem Cell in the Gut Epithelium and Enteric Nervous System

Gastroenterology ◽

10.1016/s0016-5085(12)60406-5 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-108 ◽

Cited By ~ 1

Author(s):

Michael Quante ◽

Christoph B. Westphalen ◽

Samuel Asfaha ◽

Michael D. Gershon ◽

Timothy C. Wang

Keyword(s):

Nervous System ◽

Stem Cell ◽

Neural Crest ◽

Enteric Nervous System ◽

Gut Epithelium

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Origins, migration and differentiation of glial cells in the insect enteric nervous system from a discrete set of glial precursors

Development ◽

10.1242/dev.117.1.59 ◽

1993 ◽

Vol 117 (1) ◽

pp. 59-74 ◽

Cited By ~ 1

Author(s):

P. F. Copenhaver

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Glial Cells ◽

Neuronal Migration ◽

Extended Period ◽

Enteric Neurons ◽

Distinct Population ◽

Enteric Ganglia ◽

Enteric Glial Cells ◽

Enteric Plexus

The enteric nervous system (ENS) of the moth, Manduca sexta, consists of two primary cellular domains and their associated nerves. The neurons of the anterior domain occupy two small peripheral ganglia (the frontal and hypocerebral ganglia), while a second population of neurons occupies a branching nerve plexus (the enteric plexus) that spans the foregut-midgut boundary. Previously, we have shown these two regions arise by separate programs of neurogenesis: cells that form the anterior enteric ganglia are generated from three discrete proliferative zones that differentiate within the foregut epithelium. In contrast, the cells of the enteric plexus (the EP cells) emerge from a neurogenic placode within the posterior lip of the foregut. Both sets of neurons subsequently undergo an extended period of migration and reorganization to achieve their mature distributions. We now show that prior to the completion of neurogenesis, an additional class of precursor cells is generated from the three proliferative zones of the foregut. Coincident with the onset of neuronal migration, this precursor class enters a phase of enhanced mitotic activity, giving rise to a population of cells that continue to divide as the ENS matures. Using clonal analyses of individual precursors, we demonstrate that the progeny of these cells become distributed along the same pathways taken by the migratory neurons; subsequently, they contribute to an ensheathing layer around the branches of the enteric plexus and the enteric ganglia. We conclude that this additional precursor class, which shares a common developmental origin with the enteric neurons, gives rise to a distinct population of peripheral glial cells. Moreover, the distribution of enteric glial cells is achieved by their migration and differentiation along the same pathways that are formed during the preceding phases of neuronal migration.

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