Role of Frzb-1 in Chick Melanogenesis

描述(申请人提供)：在脊椎动物胚胎发育过程中，神经元 以及周围神经系统的神经胶质细胞和色素细胞 (黑素细胞)起源于一种常见的前体细胞，即神经脊细胞。这个 神经脊细胞命运的规范必须在 以确保周围神经系统的正常发育和 色素细胞。最近，有研究表明，分泌型的异位表达 WNT信号导致色素细胞数量增加，并伴随着 神经元和神经胶质细胞数量的减少，表明Wnt信号在 在血统分离中扮演着重要的角色。然而，由于WNT通常被表达为 在神经源性和胶质源性的规范过程中，似乎有可能是额外的 为了让WNTS具体参与，需要层层监管 在特定的黑色素生成谱系中。Frzb-1、a 神经源性和非神经源性神经管中分泌的Wnt活性拮抗剂 胶质生成规范，但不是在黑色素生成规范期间，表明 FRZB-1可能在谱系调控中发挥重要作用。 我们建议检验假设Frzb-1是充分和必要的 禽类胚胎黑色素生成的抑制。如果我们的假设是正确的， 我们的结果将有助于理解细胞谱系的特性。 在胚胎发育过程中。此外，由于不适当的监管 WNT活性与恶性黑色素瘤有关，我们的研究将有所帮助 确定重要的调控回路，这些回路可能在疾病的发生或发展过程中发挥作用 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.