Postnatal Development of the Mouse Enteric Nervous System

AbstractIn mammals, neural crest cells populate the gut and form the enteric nervous system (ENS) early in embryogenesis. Although the basic ENS structure is highly conserved across species, we show important differences between mice and humans relating to the prenatal and postnatal development of mucosal enteric glial cells (mEGC), which are essential ENS components. We confirm previous work showing that in the mouse mEGCs are absent at birth, and that their appearance and homeostasis depends on postnatal colonization by microbiota. In humans, by contrast, a network of glial cells is already present in the fetal gut. Moreover, in xenografts of human fetal gut maintained for months in immuno-compromised mice, mEGCs persist following treatment with antibiotics that lead to the disappearance of mEGCs from the gut of the murine host. Single cell RNAseq indicates that human and mouse mEGCs differ not only in their developmental dynamics, but also in their patterns of gene expression.

Download Full-text

Intestinal microbiota influence the early postnatal development of the enteric nervous system

Neurogastroenterology & Motility ◽

10.1111/nmo.12236 ◽

2013 ◽

Vol 26 (1) ◽

pp. 98-107 ◽

Cited By ~ 139

Author(s):

J. Collins ◽

R. Borojevic ◽

E. F. Verdu ◽

J. D. Huizinga ◽

E. M. Ratcliffe

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Postnatal Development ◽

Intestinal Microbiota ◽

Early Postnatal Development

Download Full-text

A120 INFLUENCE OF THE MICROBIOTA ON THE POSTNATAL DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM IS DEPENDENT ON MOUSE STRAIN

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.119 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 140-141

Author(s):

J Huang ◽

J Popov ◽

F Markovic ◽

E Ratcliffe

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Postnatal Development ◽

Mouse Strain ◽

Host Response ◽

Inbred Mouse Strain ◽

Neuronal Cell ◽

Postnatal Life ◽

Neuronal Marker ◽

Nih Swiss

Abstract Background Gastrointestinal function depends on the normal formation of the enteric nervous system (ENS) during fetal and postnatal development. Prior research in an outbred strain of mice (NIH Swiss) has shown that the absence of the gut microbiome in germ-free (GF) mice results in morphological and functional abnormalities of the ENS compared to specific pathogen free (SPF) mice, including an alteration in proportion of nitrergic neurons. Increasing research has been suggesting that the genetic background of the host can impact the host response to the GF state. Aims We tested the hypothesis that the absence of the microbiome in an inbred mouse strain (C57BL/6) could influence the development of the ENS during early postnatal life. Methods C57BL/6 GF and SPF mice were sacrificed at postnatal day 3 (P3) and P28 (n=4–5 per group). Ileum and colon were collected at P3 and P28 and processed for whole mount preparations. The neuronal network in the myenteric plexus was visualized by immunohistochemistry using antibodies against the pan-neuronal marker PGP9.5. Neuronal cell bodies and nitrergic neurons were identified by immunolabeling with antibodies to the neuronal marker HuC/D and to neuronal nitric oxide (nNOS). Nerve fibre density was quantified by measuring the percentage of PGP9.5-positive pixels (μm2) compared to the whole field using an image analysis program (Volocity; reported as %). Proportions of nitrergic to myenteric neurons were determined by manually counting (blinded) the number of nNOS-positive neurons and dividing by the total number of HuC/D-positive cells per field (reported as %). Results We found a significant increase in nerve density at P3 in the GF compared to SPF mice in both ileum (43% vs. 37%; p=0.03) and colon (45% vs. 39%; p=0.03). No significant differences, however, were identified between GF and SPF mice at P28 in either ileum (27% vs. 25%; n.s.) or colon (31% vs. 32%; n.s.). At P3, no significant differences in proportion of nitrergic neurons were seen in the GF compared to SPF ileum (27% vs. 27%; n.s.). Conclusions In contrast to earlier observations in the NIH Swiss mice, in which GF mice had decreased nerve density and an increase in nitrergic neurons at P3, our findings reveal an opposite response in nerve density in the C57BL/6 mice and no change in nitrergic neurons. These results suggest that the genetic strain of the mouse model can influence the host response to changes in the microbiome. Further studies are needed to further elucidate potential underlying mechanisms. Funding Agencies NSERC

Download Full-text