SOLUBLE AND CELL-BOUND FORMS OF STEEL FACTOR ACTIVITY PLAY DISTINCT ROLES IN MELANOCYTE PRECURSOR DISPERSAL AND SURVIVAL ON THE LATERAL NEURAL CREST MIGRATION PATHWAY
B. Wehrlehaller et Ja. Weston, SOLUBLE AND CELL-BOUND FORMS OF STEEL FACTOR ACTIVITY PLAY DISTINCT ROLES IN MELANOCYTE PRECURSOR DISPERSAL AND SURVIVAL ON THE LATERAL NEURAL CREST MIGRATION PATHWAY, Development, 121(3), 1995, pp. 731-742
Trunk neural crest cells segregate from the neuroepithelium and enter
a 'migration staging area' lateral to the embryonic neural tube, After
some crest cells in the migration staging area have begun to migrate
on a medial pathway, a subpopulation of crest-derived cells remaining
in the migration staging area expresses mRNAs for the receptor tyrosin
e kinase, c-kit, and tyrosinase-related protein-2, both of which are c
haracteristic of melanocyte precursors. These putative melanocyte prec
ursors are subsequently observed on the lateral crest migration pathwa
y between the dermatome and overlying epithelium, and then dispersed i
n nascent dermal mesenchyme. Melanocyte precursors transiently require
the c-kit ligand, Steel factor for survival. Although Steel factor mR
NA is transiently expressed in the dorsal dermatome before the onset o
f trunk neural crest cell dispersal on the lateral pathway, it is no l
onger produced by dermatomal cells when melanocyte precursors have dis
persed in the dermal mesenchyme. To assess the role of Steel factor in
migration of melanocyte precursors on the lateral pathway, we analyze
d melanocyte precursor dispersal and fate on the lateral pathway of tw
o different Sl mutants, Sl, a null allele, and Sl(d), which lacks cell
surface-associated Steel factor but produces a soluble form. No melan
ocyte precursors were detected in the dermatome of embryos homozygous
for the Sl allele or in W mutants that lack functional c-kit. In contr
ast, in embryos homozygous for the Sl(d) allele, melanocyte precursors
appeared on the lateral pathway, but subsequently disappear from the
dermis. These results suggest that soluble Steel factor is required fo
r melanocyte precursor dispersal on the lateral pathway, or for their
initial survival in the migration staging area. In contrast, membrane-
bound Steel factor appears to promote melanocyte precursor survival in
the dermis.