Introduction
The enteric nervous system (ENS) controls intestinal motility,
regulates mucosal secretion and modulates intestinal blood flow.
It also responds to sensory stimuli from the intestinal lumen and
the wall of the gut. Performing these functions requires a
complex network of interacting neurons and glial cells. These
cells are derived from the vagal, sacral and upper thoracic neural
crest. To create the ENS, neural crest precursors migrate into
the gut during embryonic development. During the process of
migration, these cells actively proliferate. Precursors cells
then differentiate into neurons and glia, extend processes and
further differentiate to specific neuronal subtypes.
While many genes products are already
known to influence ENS development,
there is currently incomplete information about the
molecular mechanisms that are essential to form the ENS.
We have therefore initiated a screen for novel mutations that
affect ENS development in collaboration with
The Jackson Laboratory.
The ENS of mutant
mice generated by ENU mutagenesis will be evaluated using
whole mount
acetylcholinesterase and NADPH diaphorase staining. These
methods allow the plexus of neurons within the ENS to be viewed
along the entire length of the bowel and are
sensitive ways to look for mutations
that affect neuronal migration, neuron density,
and neuronal process outgrowth.
As mice are analyzed, the phenotype will be
posted to the web site along with pictures of
any abnormal ENS variants found. Novel phenotypic variants will
be further characterized to determine the gene mutation that
causes the observed phenotype. All mice will be made freely
available to the scientific community as soon as possible.
