Multiple Actions of Stem Cell Factor in Neural Crest Cell Differentiationin Vitro

Abstract

The neural crest is a transient tissue of the vertebrate embryo that gives rise to most primary sensory neurons and pigment cells in the adult organism, among other cell types and tissues. Many neural crest cells are pluripotent in the sense that their progeny can generate more than one phenotype. The presence of pluripotent neural crest cell-derived cells at sites of terminal differentiation suggests that location-specific cues from the embryonic environment, such as growth factors, are involved in directing their survival, proliferation, and cell type specification. We have therefore examined the influences of one pertinent growth factor, stem cell factor (SCF), on neural crest cell development by in vitro colony assay in a serum-free culture medium. SCF showed three major effects. (1) SCF is trophic for early neural crest cells, that is, either pluripotent cells and/or their more mature progeny. This effect occurs only if SCF is present throughout the culture period, and it is not observed when a neurotrophin is present in addition to SCF. (2) More colonies contain sensory neuron precursors in the presence of SCF. This effect is neutralized by NGF and neurotrophin-3 (NT-3), but not by brain-derived neurotrophic factor (BDNF). (3) The combination of SCF and any neurotrophin tested (NGF, BDNF, NT-3) is trophic for melanogenic cells, whereas SCF alone does not detectably affect melanogenesis. This suggests either that both types of factor are required for melanotrophic action or that melanogenic cells become dependent on neurotrophins after exposure to SCF. Our observation that SCF is required during the first half of the culture period only, and NGF during the second half only, indicates the latter possibility. Whereas coat color changes in the mouse mutants W (c-kit defect) and Steel (SCF defect) and several in vivo and in vitro studies by other investigators have shown previously that SCF is melanotrophic, they also indicated the requirement of an additional factor, or factors, in melanogenesis. Our data suggest that SCF affects neural crest cell development at multiple levels and that survival of melanogenic cells is mediated by a combination of SCF and a neurotropin, rather than by SCF alone.

Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype

“…Because our results suggested that hypoxia-treated NB cells lose their sympathetic ganglionic phenotype, we examined the effects of hypoxia on expression of neural crest genes. Id2, Notch-1, HES-1, and c-kit are involved in determination of neural crest cell fate (35)(36)(37)(38) and are expressed in sympathetic precursor cells at earlier developmental stages than, for instance, N-myc, HASH-1, and dHAND (21). We observed Id2 expression in all four tested cell lines, and this expression decreased with time in culture.…”

Deconstructing evolution of adult phenotypes: genetic analyses ofkitreveal homology and evolutionary novelty during adult pigment pattern development ofDaniofishes

“…kit has been implicated in survival, proliferation, differentiation and migration in melanophore or melanocyte lineages, with different studies emphasizing different primary roles depending on the particular stage and system (Reid et al, 1995;Wehrle-Haller and Weston, 1995;Bernex et al, 1996;Langtimm-Sedlak et al, 1996;Yoshida et al, 1996;Mackenzie et al, 1997;Parichy et al, 1999;Kelsh et al, 2000). Recent studies have demonstrated requirements for zebrafish kit in embryonic melanophore migration and survival (Rawls and Johnson, 2003), for population expansion during larval melanophore regeneration (Yang et al, 2004;Yang and Johnson, 2006), and during terminal differentiation of regenerating fin melanophores as well as larval melanophores when their development is delayed experimentally (Rawls and Johnson, 2000;Mellgren and Johnson, 2004).…”

Melanoma and the Nervous System – Novel Pathways Mediated by Neurotrophins and Their Receptors

“…Epidermalrestricted NCSC express all NTs, while NGF and NT-3 support their proliferation as well as survival of daughter cells, in that NGF and NT-3 depletion results in loss of 70% and 60% neurons, respectively (Dasari et al, 2008;Zhang et al, 1997). Moreover, NTs can either support proliferation or induce apoptosis in NCC, depending on their lineage/differentiation stage (Langtimm-Sedlak et al, 1996). Consistently, different expression of trk receptors may identify distinct subpopulations of early NCC.…”