Role of Frzb-1 in Chick Melanogenesis

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DESCRIPTION (provided by applicant): During vertebrate embryogenesis, neurons and glia of the peripheral nervous system as well as pigment cells (melanocytes) descend from a common progenitor cell, the neural crest cell. The specification of neural crest cell fates must be exquisitely controlled in order to ensure the proper development of the peripheral nervous system and pigment cells. Recently, it has been shown that ectopic expression of secreted Wnt signals causes an increase in the number of pigment cells accompanied by a decrease in the number of neurons and glia, suggesting that Wnt signals play an important role in lineage segregation. However, as Wnts are normally expressed during neurogenic and gliogenic specification, it seems likely that additional layers of regulation are required in order for Wnts to specifically participate in the specification of melanogenic lineages. The expression of Frzb-1, a secreted antagonist of Wnt activity, in the neural tube during neurogenic and gliogenic specification, but not during melanogenic specification, suggests the possibility that Frzb-1 plays an important role in the regulation of lineage. We propose to test the hypothesis that Frzb-1 is sufficient and necessary for the inhibition of melanogenesis in avian embryos. If our hypothesis is correct, our results will contribute to an understanding of cell lineage specification during embryonic development. In addition, as the inappropriate regulation of Wnt activity has been implicated in malignant melanomas, our studies will help identify important regulatory circuits that may play a role in the genesis or progression of malignant melanomas.