The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos.
The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos.
复制标题
DOI：
--
复制
发表时间：
2001-04
期刊：
影响因子：
4.6
通讯作者：
Robert Kos;M. Reedy;Randy L. Johnson;C. Erickson
中科院分区：
文献类型：
--
作者：
Robert Kos;M. Reedy;Randy L. Johnson;C. Erickson
翼状螺旋或叉头类转录因子已被证明在细胞特化和谱系分离中起重要作用。我们已经克隆了鸡同源的FoxD 3，翼螺旋类转录因子的成员，并分析其表达。基于其在背侧神经管和所有神经嵴谱系中的表达，除了晚期迁移的成黑素细胞，我们预测FoxD 3可能是重要的神经嵴谱系从神经上皮分离，并抑制早期迁移的神经嵴细胞中的黑素生成。FoxD 3的错误表达，在神经嵴发育早期的侧神经上皮电穿孔HNK 1免疫反应性在整个神经上皮细胞的扩张，虽然这些细胞没有经历上皮/间充质转化。为了测试FoxD 3是否抑制早期迁移的神经嵴细胞中的黑素生成，我们用反义寡核苷酸敲低了培养的神经嵴中的表达，并通过用吗啉代反义寡核苷酸治疗在体内敲低了表达。这两种实验方法都导致了成黑素细胞谱系的扩张，可能是以神经元和神经胶质谱系为代价的。相反，使用RCAS病毒在晚期迁移的神经嵴细胞中持续表达FoxD 3导致成黑素细胞发育失败。我们认为FoxD 3在神经嵴发育中起两个重要作用。首先，它参与神经嵴谱系与神经上皮的分离。其次，它抑制黑素生成，从而允许其他神经嵴衍生物在神经嵴形成的早期阶段分化。
The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.