Enteric nervous system development: what could possibly go wrong?

Abstract

The gastrointestinal tract contains its own set of intrinsic neuroglial circuits - the enteric nervous system (ENS) - which detects and responds to diverse signals from the environment. Here, we address recent advances in the understanding of ENS development, including how neural-crest-derived progenitors migrate into and colonize the bowel, the formation of ganglionated plexuses and the molecular mechanisms of enteric neuronal and glial diversification. Modern lineage tracing and transcription-profiling technologies have produced observations that simultaneously challenge and affirm long-held beliefs about ENS development. We review many genetic and environmental factors that can alter ENS development and exert long-lasting effects on gastrointestinal function, and discuss how developmental defects in the ENS might account for some of the large burden of digestive disease.

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

“…It also regulates nutrient and water absorption and interacts with the immune and endocrine cells in the gut . The ENS consists of two major ganglionated plexuses, the myenteric plexus and the submucosal plexus, which develop from embryonic day 8 to postnatal day 14 in mice and from week 4 in human embryos to the postnatal period . Neural crest‐derived cells migrate to and colonise the bowel, giving rise to the ENS.…”

“…However, more recent studies suggest that the ENS in adult mice is capable of maturation and plasticity, and that neurogenesis of enteric neurones can occur . Studies suggest that 5‐HT stimulates enteric neurogenesis, and modulation of 5‐HT levels during ENS development may therefore have long‐lasting effects on the ENS function . By contrast to the enteric neurones, which are only located in the enteric ganglia, enteric glial cells are present within the interganglionic fiber tracts, the smooth muscle layers and the lamina propria of the mucosa .…”

“…Failure of neural crest‐derived cells to colonise the bowel results in Hirschsprung disease, a life‐threatening disease with an incidence of approximately one in 5000 births . Premature differentiation of progenitors into neurones or glial cells impairs the colonisation of neural crest‐derived cells in the distal bowel, and patients with Hirschsprung disease are missing enteric neurones along a variable length of the intestine.…”

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

“…Enteric glial cells are a further subset of peripheral glia that reside in the intestinal wall, where they have multiple and diverse roles in maintaining the intestinal barrier, controlling intestinal motility and supporting enteric neuronal function and survival, all processes that are critical for the function of the gut. Morphologically distinct populations exist in different regions of the gut but the true diversity and functions of many of these cells remains unknown (Coelho‐Aguiar Jde et al, ; Grubisic & Gulbransen, ; Rao & Gershon, ; Ruhl, ). A further class of peripheral nerve glial are olfactory ensheathing cells, which envelop olfactory axons in both the CNS and PNS (Barraud et al, ; Higginson & Barnett, ; Ramon‐Cueto & Avila, ).…”

“…While poorly understood, increasing evidence indicates SGCs modulate the neuronal environment and regulate neuronal activity within the ganglia (Hanani, 2010(Hanani, , 2012Suadicani et al, 2010;Takeda, Takahashi, & Matsumoto, 2009) processes that are critical for the function of the gut. Morphologically distinct populations exist in different regions of the gut but the true diversity and functions of many of these cells remains unknown (Coelho-Aguiar Jde et al, 2015;Grubisic & Gulbransen, 2017;Rao & Gershon, 2018;Ruhl, 2005). A further class of peripheral nerve glial are olfactory ensheathing cells, which envelop olfactory axons in both the CNS and PNS (Barraud et al, 2010;Higginson & Barnett, 2011;Ramon-Cueto & Avila, 1998).…”