An ultrastructural analysis of the developing enteric nervous system of the guinea-pig small intestine

Abstract

SummaryThe developing enteric nervous system of the guinea-pig has been analysed uttrastructurally. In addition, electron microscope autoradiography, following incubation with tritiated 5-hydroxytryptamine ([3H]5-HT) or tritiated norepinephrine ([3H]NE) was used to locate the developing axons of enteric serotoninergic and adrenergic neurons respectively. Observations have been correlated with previous studies of the development of the various types of enteric neuron and the onset of intestinal neuromuscular function. Prior to 25 days of gestation no neurons can be recognized morphologically. Neurons first appear at 25 days' gestation, together with a primitive neuropil in neural islands within the outer gut mesenchyme. Ganglion cell precursors are primitive at first and resemble the cells in the surrounding mesenchyme. Growth cones are abundant but there are no terminal varicosities or synapses. The circular muscle als0 begins to form at this time. At 32 days' gestation the longitudinal layer of smooth muscle can be discerned and, within the myenteric plexus, terminal axonal varicosities appear containing small (about 50 nm in diameter) electron-lucent synaptic vesicles.The submucosal plexus appears to be derived from neurons and neurites that reach it from the earlier-developing myenteric plexus. The submucosal plexus can be recognized at 38 days of gestation but is not well developed until day 42. Synapses on ganglion cell somata first appear in the myenteric plexus on gestational day 38 and are numerous on day 42 when the first axo-dendritic synapses can be seen. Between days 42 and 48 the developing neural tissue and growing smooth muscle cells interdigitate but after day 48, the plexus becomes ensheathed by supporting cells and connective tissue and this interdigitation is lost. Prior to day 48 most varicosities contain small electron-lucent synaptic vesicles; however, after this time a variety of terminals appears. Between days 48 and 53 of gestation evidence of degenerating neuronal processes is common, indicating that cell death may occur. Electron microscopic autoradiography with [3H]5-HT reveals labelling of axons in the neuropil of the myenteric plexus at day 32 of gestation. Some primitive appearing cell bodies, however, are also labelled and these cells seem to be entering the myenteric pIexus from the surrounding mesenchyme.

Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons

“…Subsequently, 5-HT 4 receptors were demonstrated to be neuroprotective and to promote the development of new neurons from adult stem cells (Liu et al, 2009). Because enteric neurons are born asynchronously (Pham et al, 1991) and serotonergic neurons are among the first to arise (Pham et al, 1991; Blaugrund et al, 1996; Chalazonitis et al, 2008), it follows that serotonergic neurons coexist with dividing ENCDCs, some of which receive synapses (Gershon et al, 1981). It is thus plausible that serotonergic input influences the fate of ENCDCs; these precursors express SERT and 15 subtypes of 5-HT receptor.…”

Neurochemical differentiation of rat enteric neurons during pre- and postnatal life

“…Recently, however, it was suggested that these crest-derived cells are multipotent (Rothman et al 1990 and that their subsequent differentiation is influenced by enteric microenvironmental factors (Le Douarin and Dulac 1992; Rothman et al 1990;Newgreen and Hartley, 1995). The ENS ontogeny has been studied in mammals (Gershon et al 1981; Saffrey and Burnstock 1988;Pham et al 1991;Gershon et al 1993;Timmermans et al 1994;Belai et al 1995;Ward and Torihashi 1995;Newgreen and Hartley 1995). It seems that full maturity is not yet reached at birth, while a functional innervation is already present in foetal life (Gershon and Thompson 1973).…”

VIP-Immunoreactive Nerve Structures of the Gastrointestinal Tract in the Developing and Adult Domestic Duck.

“…Moreover, during these 13-17 days, the circular muscle layer develops in the gut of chick embryos; it could play a role in the neuronal growth, as reported above (SAFFREY and BURNSTOCK, 1988). On the other hand, the appearance of a specific phenotype in embryonal gastrointestinal neurons precedes by a fairly long time the assumption of a definitive functional role, as hypothesized for peptidergic and cholinergic neurons in the caecum and ileum of the guinea pig embryo (GINTZLER et al, 1980;GERSHON et al, 1981;SAFFREY and BURNSTOCK, 1988).…”