Colonization of the developing murine enteric nervous system and subsequent phenotypic expression by the precursors of peptidergic neurons

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Abstract
The development of peptidergic neurons was analyzed in the murine bowel. Neurons, detected immunocytochemically with antisera to substance P (SP) and vasoactive intestinal polypeptide (VIP), respectively, were selected for study. Explantation of the primordial bowel with subsequent growth in organotypic tissue culture served as an assay for the presence of neuronal precursor cells within the developing gut. One objective of the study was to determine whether the neural crest population that initially colonizes the mammalian bowel contains the precursors of peptidergic neurons as well as those of neurons that contain small molecule neurotransmitters, or whether peptidergic neurons are derived from a later migration of émigrés to the gut. A second objective was to compare the timing of peptidergic phenotypic expression with that of the small molecule neurotransmitters, acetylcholine (ACh) and serotonin (5-HT). The precursors of peptidergic neurons were found to have colonized the bowel prior to the appearance of recognizable neurons of any type. The immunocytochemical detection of SP and VIP in vivo lagged behind the appearance of cholinergic and serotonergic markers by at least 2 days in the foregut and by greater than 3 days in the hindgut. Peptidergic neurons showed a proximodistal pattern of phenotypic expression. These observations support the hypothesis that the murine bowel is colonized by a single wave of precursor cells that contains the primordia of peptidergic neurons as well as neurons that use small molecule neurotransmitters. Data are consistent with the earlier expression of the small molecule phenotype. The proximodistal sequence of phenotypic expression in the absence of a similar sequence in precursor colonization supports an interaction between the precursors of enteric neurons and the microenvironment of the gut that modulates neuronal phenotypic expression.