Biology Reference
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abnormal manner, i.e., the cells get stuck in dorsal positions, where dorsal
root ganglia will form, and ventral migration is impaired. Consequently, the
sympathetic nervous system of the trunk is severely hypoplastic. A particular
Nrg1 isoform, the type I isoform, provides the signal required for the
migration of sympathogenic neural crest cells, and is expressed at the origin,
along the migratory path and at the migration target of sympathogenic neural
crest cells. The survival of neural crest cells during migration to the anlage of
the sympathetic nervous system is not affected by the Nrg1, ErbB2 or ErbB3
mutations. The observed changes can therefore be attributed to an altered
motility or directional migration of the neural crest cells (Britsch et al., 1998).
Schwann cell precursors are also impaired in their development in Nrg1,
ErbB2 or ErbB3 mutant mice. At E10 in the mouse, such glial progenitors can
be observed to line peripheral axon bundles, but they do not yet express
markers seen in Schwann cells, and instead express genes characteristic of
neural crest cells. Thus, the cells are identifiable as Schwann cells progenitors
only through their position, the association with the outgrowing axons. In
Nrg1, ErbB2 or ErbB3 mutant mice, numbers of neural crest cells that line
peripheral axons are already severely diminished at E10. The mechanism by
which this arises has not been characterized in detail. Later during
development, Nrg1 plays a prominent role as a growth and survival factor
for Schwann cell precursors. However, whether aberrant growth/survival is
the mechanism that underlies the changed development of gliogenic neural
crest cells in Nrg1, ErbB2 or ErbB3 mutant mice is less clear. Defective
migration, i.e., an inability of neural crest cells to move out of dorsal root
ganglia and to migrate along axon bundles, may be responsible or, at least,
contribute. The isoform that is essential for the development of gliogenic
neural crest cells corresponds to type III Nrg1, which is produced by neurons
and inserted into the axonal membrane. Axonally presented Nrg1 stimulates
thus the development of gliogenic neural crest cells (Meyer et al., 1997).
Sox10 controls the expression of ErbB3 during development of
neural crest cells
In wildtype mice, Sox10 and ErbB3 are expressed in similar patterns in neural
crest cells. We therefore tested whether the two genes interact genetically
(Britsch et al., 2001). This became possible since a spontaneous mutation of
Sox10, the Sox10
Dom
allele, was identified in mice (Southard-Smith et al.,
1998). The frameshift mutation present in the Sox10
Dom
allele allows the
production of a mutant mRNA that can be detected by in situ hybridization,
which does however not allow the generation of a functional Sox10 protein.
When ErbB3 is used as a probe to detect neural crest cells in Sox10 mutant
mice, a marked downregulation of ErbB3 expression is apparent. Other genes
