Melanocyte fate in neural crest is triggered by Myb proteins through activation of c-kit.
The c-myb proto-oncogene and its oncogenic derivative v-mybAMV encode transcriptional regulators engaged in the commitment of hematopoietic cells. While the c-Myb protein is important for the formation and differentiation of various progenitors, the v-MybAMV oncoprotein induces in chicks a progression and transformation of the single (monoblastic) cell lineage. Here we present the first evidence of cell fate-directing abilities of c-Myb and v-MybAMV proteins in avian neural crest (NC), where both proteins determine melanocytogenesis. The increased concentration of c-Myb induces progression into dendritic melanocytes and differentiation. The v-myb oncogene converts essentially all NC cells into melanocytes and causes their transformation. Both Myb proteins activate in NC cells expression of the c-kit gene and stem cell factor c-Kit signaling--one of the essential pathways in melanocyte development. These observations suggest that the c-myb-c-kit pathway represents a common regulatory scheme for both hematopoietic and neural progenitors and establishes a novel experimental model for studies of melanocytogenesis and melanocyte transformation.
Karafiat
V
V
Department of Molecular Virology, Institute of Molecular Genetics, AS CR v.v.i., Vídenská 1083, Prague 4, 14220, Czech Republic.
Dvorakova
M
M
Pajer
P
P
Cermak
V
V
Dvorak
M
M
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002642:Chick Embryo; D017931:DNA Primers / Q000235:genetics; D020570:Genes, myb; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D020626:Oncogene Proteins v-myb / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D020626:Oncogene Proteins v-myb; D020598:Proto-Oncogene Proteins c-myb; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit