At the onset of their migration into the embryo, many neural crest
cells are pluripotent in the sense that
they have the capacity to generate progeny that consist of more than one
cell type. More recently, we have
found that there are pluripotent neural crest cell-derived cells even at
sites of terminal differentiation. These
findings support the notion that cues originating from the microenvironment,
at least in part, direct neural
crest cell type specification. Based on the rationale that growth factors
that
are known to support survival of
neural crest cell derivatives may have additional functions in progenitor
cell development, we have examined
the action of pertinent growth factors. Trophic, mitogenic, antiproliferative
and differentiation promoting
activities were found. Stem cell factor (SCF) is trophic for pluripotent
neural crest cells. Contrary to
expectation, SCF plus a neurotrophin, rather than SCF alone, is trophic
for
committed melanogenic cells.
Basic fibroblast growth factor (bFGF) is mitogenic both for pluripotent
cells
and committed melanogenic
cells. However, the cells become dependent on another factor for survival.
Whereas any neurotrophin tested
can rescue bFGF-activated pluripotent neural crest cells, the factor that
rescues melanogenic cells remains to
be determined. Transforming growth factor β1 (TGF-β1) is a
powerful antimitotic signal for all neural crest
cells that overrides the bFGF/neurotrophin proliferative signal. Furthermore,
SCF promotes differentiation
of neural crest cells into cells of the sensory neuron lineage.
Neurotrophin-3 (NT-3) specifically promotes
high affinity uptake of norepinephrine by neural crest cells and is thus
thought to play a critical role in the
differentiation of sympathetic neuroblasts. In summary, our data indicate
that neurotrophins and other
pertinent growth factors affect survival, proliferation and differentiation
of
neural crest cells at multiple
levels and in different lineages. Moreover, our findings emphasise the
importance of the concerted action of
combinations of growth factors, rather than of individual factors.
