Enteric glia as a source of neural progenitors in adult zebrafish
- The Francis Crick Institute, United Kingdom
- University of Bath, United Kingdom
- AstraZeneca, United Kingdom
Abstract
The presence and identity of neural progenitors in the enteric nervous system (ENS) of vertebrates is a matter of intense debate. Here we demonstrate that the non-neuronal ENS cell compartment of teleosts shares molecular and morphological characteristics with mammalian enteric glia but cannot be identified by the expression of canonical glia markers. However, unlike their mammalian counterparts, which are generally quiescent and do not undergo neuronal differentiation during homeostasis, we show that a relatively high proportion of zebrafish enteric glia proliferate under physiological conditions giving rise to progeny that differentiate into enteric neurons. We also provide evidence that, similar to brain neural stem cells, the activation and neuronal differentiation of enteric glia are regulated by Notch signalling. Our experiments reveal remarkable similarities between enteric glia and brain neural stem cells in teleosts and open new possibilities for use of mammalian enteric glia as a potential source of neurons to restore the activity of intestinal neural circuits compromised by injury or disease.
Data availability
High-throughput sequencing data have been deposited in GEO under accession codes GSE145885.
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Expression analysis of adult zebrafish enteric nervous systemNCBI Gene Expression Omnibus, GSE145885.
Article and author information
Author details
Funding
The Francis Crick Institute (core funding)
- Vassilis Pachnis
BBSRC (BB/L022974/1)
- Vassilis Pachnis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were carried out in compliance with the Animals (Scientific Procedures) Act 1986 (UK) and in accordance with the regulatory standards of the UK Home Office (Project Licence PCBBB9ABB). Experimental protocols were approved by the local Animal Welfare and Ethical Review Body (AWERB) of the Francis Crick Institute.
Copyright
© 2020, McCallum et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Enteric glia as a source of neural progenitors in adult zebrafish
eLife 9:e56086.
https://doi.org/10.7554/eLife.56086
Further reading
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- Developmental Biology
Correct intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior. The LR asymmetry of the DM also governs blood and lymphatic vessel formation for the digestive tract, which is essential for prenatal organ development and postnatal vital functions including nutrient absorption. Although the genetic LR asymmetry of the DM has been extensively studied, a divider between the left and right DM has yet to be identified. Setting up LR asymmetry for the entire body requires a Lefty1+ midline barrier to separate the two sides of the embryo, without it, embryos have lethal or congenital LR patterning defects. Individual organs including the brain, heart, and gut also have LR asymmetry, and while the consequences of left and right signals mixing are severe or even lethal, organ-specific mechanisms for separating these signals remain poorly understood. Here, we uncover a midline structure composed of a transient double basement membrane, which separates the left and right halves of the embryonic chick DM during the establishment of intestinal and vascular asymmetries. Unlike other basement membranes of the DM, the midline is resistant to disruption by intercalation of Netrin4 (Ntn4). We propose that this atypical midline forms the boundary between left and right sides and functions as a barrier necessary to establish and protect organ asymmetry.
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- Developmental Biology
Numerous reports showed that the epididymis plays key roles in the acquisition of sperm fertilizing ability but its contribution to embryo development remains less understood. Female mice mated with males with simultaneous mutations in Crisp1 and Crisp3 genes exhibited normal in vivo fertilization but impaired embryo development. In this work, we found that this phenotype was not due to delayed fertilization, and it was observed in eggs fertilized by epididymal sperm either in vivo or in vitro. Of note, eggs fertilized in vitro by mutant sperm displayed impaired meiotic resumption unrelated to Ca2+ oscillations defects during egg activation, supporting potential sperm DNA defects. Interestingly, cauda but not caput epididymal mutant sperm exhibited increased DNA fragmentation, revealing that DNA integrity defects appear during epididymal transit. Moreover, exposing control sperm to mutant epididymal fluid or to Ca2+-supplemented control fluid significantly increased DNA fragmentation. This, together with the higher intracellular Ca2+ levels detected in mutant sperm, supports a dysregulation in Ca2+ homeostasis within the epididymis and sperm as the main factor responsible for embryo development failure. These findings highlight the contribution of the epididymis beyond fertilization and identify CRISP1 and CRISP3 as novel factors essential for sperm DNA integrity and early embryo development.
