How Smooth Muscle Contractions Shape the Developing Enteric Nervous System.

Nicolas R Chevalier,Yanis Ammouche,Sylvie Dufour,Richard J Amedzrovi Agbesi

doi:10.3389/fcell.2021.678975

Abstract

Neurons and glia of the enteric nervous system (ENS) are constantly subject to mechanical stress stemming from contractions of the gut wall or pressure of the bolus, both in adulthood and during embryonic development. Because it is known that mechanical forces can have long reaching effects on neural growth, we investigate here how contractions of the circular smooth muscle of the gut impact morphogenesis of the developing fetal ENS, in chicken and mouse embryos. We find that the number of enteric ganglia is fixed early in development and that subsequent ENS morphogenesis consists in the anisotropic expansion of a hexagonal honeycomb (chicken) or a square (mouse) lattice, without de-novo ganglion formation. We image the deformations of the ENS during spontaneous myogenic motility and show that circular smooth muscle contractile waves induce longitudinal strain on the ENS network; we rationalize this behavior by mechanical finite element modeling of the incompressible gut wall. We find that the longitudinal anisotropy of the ENS vanishes when contractile waves are suppressed in organ culture, showing that these contractile forces play a key role in sculpting the developing ENS. We conclude by summarizing different key events in the fetal development of the ENS and the role played by mechanics in the morphogenesis of this unique nerve network.

Highlights

The enteric nervous system (ENS) is a network of neural, glial and progenitor cells embedded inside the wall of the gastro-intestinal tract, that governs both the mechanical and chemical activity of the intestine (Costa et al, 2000)
As from embryonic day 8, the chicken GI tract is entirely colonized by enteric neural crest cells (ENCCs); in the myenteric plexus (Figure 1A), these cells have condensed to ganglia connected to each other by inter-ganglionic fibers
We further found that the ENS mesh becomes more elongated along the longitudinal direction, as shown by measuring the aspect ratio of inter-ganglionic spaces from E8 to E16 (Figure 1D)

Summary

Introduction

The enteric nervous system (ENS) is a network of neural, glial and progenitor cells embedded inside the wall of the gastro-intestinal tract, that governs both the mechanical and chemical activity of the intestine (Costa et al, 2000). It originates from the migration of enteric neural crest cells (ENCCs) inside the developing gut during early embryogenesis. The ENS is comprised of two plexuses, the myenteric and submucosal plexus. Each plexus is comprised of a mesh network of glial, neural and progenitor neural crest cells condensed in ganglia, that are interconnected by inter-ganglionic, axonal nerve fibers. The myenteric plexus is sandwiched between the longitudinal and the circular smooth layer, and projects neurites to smooth

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