Role of Frzb-1 in Chick Melanogenesis

描述（由申请人提供）：在脊椎动物胚胎发生期间，神经元 和周围神经系统的神经胶质以及色素细胞 （黑素细胞）来自一个共同的祖细胞，神经嵴细胞。的 神经嵴细胞命运的特化必须被精细地控制， 为了确保周围神经系统的正常发育， 色素细胞最近，已经表明分泌性的异位表达 Wnt信号导致色素细胞数量增加， 神经元和神经胶质细胞数量减少，表明Wnt信号在神经元和神经胶质细胞中起作用。 在种族隔离中的重要作用。然而，由于Wnt通常表达为 在神经源性和胶质源性特化过程中，似乎可能额外的 为了让Wnt具体参与， 在黑素生成谱系的规范。Frzb-1，a 分泌的Wnt活性拮抗剂，在神经原性和 胶质细胞生成的特化，而不是在黑素生成的特化，表明 Frzb-1可能在谱系调控中起重要作用。 我们建议检验Frzb-1是充分和必要的假设， 抑制鸟类胚胎中的黑素生成。如果我们的假设正确， 我们的研究结果将有助于理解细胞谱系特化 在胚胎发育期间。此外，由于不适当的管制， Wnt活性与恶性黑色素瘤有关，我们的研究将有助于 确定可能在起源中发挥作用的重要调节回路， 恶性黑色素瘤的进展。

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.