Developmental Divergence
of the
Enteric and Sympathetic Nervous Systems
In the peripheral nervous system, enteric and sympathetic
neurons develop from multipotent crest cells. While local
environmental signals in the gut and in the region of
the sympathetic ganglia play a role in the choice of cell
fate, little is known about the mechanisms that underlie
restriction to specific neuronal phenotypes. We investigated
the divergence and restriction of the enteric and sympathetic
neuronal lineages using immuno-isolated neural crest-derived
cells from the gut and sympathetic ganglia. Analysis of
neuronal and lineage-specific mRNAs and proteins indicated
that neural- crest-derived cells from the gut and sympathetic
ganglia had initiated neuronal differentiation and phenotype
divergence by E14.5. We investigated the developmental
potential of these cells using expression of tyrosine
hydroxlase as a marker for sympathetic phenotype. Tyrosine
hydroxlase expression was examined in neurons that developed
from sympathetic and enteric neuroblasts under the following
culture conditions: culture alone; co-culture with gut
monolayers to promote oradrenergic differentiation; or
co-culture with dorsal aorta monolayers to promote noradrenegeric
differentiation. Both enteric and sympathetic neuroblasts
displayed developmental plasticity at E14.5. Sympathetic
neuroblast down-regulated tyrosine hydroxlase in response
to signals from the gut environment and enteric neuroblasts
increases expression of tyrosine hydroxlase when grown
on dorsal aorta or in the absence of other cell typeis.
Tracking of individual sympathetic cells displaying a
neuronal morphology at the time of plating indicated that
neuroblasts retained phenotypic plasticity even after
initial neuronal differentiation had occurred. By E19.5
both enteric and sympathetic neuroblasts had undergone
a significant loss of their developmental potential, with
most neuroblasts retaining their lineage- specific phenotype
in all environments tested. Together our data indicate
that the developmental potential of enteric and sympathetic
neuroblasts becomes restricted over time and that this
restriction takes place not as a consequence of initial
neuronal differentiation but during the period of neuronal
maturation. Further we have characterized a default pathway
of adrenergic differentiation in the enteric nervous system
and have defined a transient requirement for gut-derived
factors in the maintenance of the enteric neuronal phenotype.
