Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell-like progenitor cells in the chick ciliary marginal zone
Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell-like progenitor cells in the chick ciliary marginal zone
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DOI：
10.1242/dev.029272
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发表时间：
2009-06-01
期刊：
影响因子：
4.6
通讯作者：
Nakagawa, Shinichi
中科院分区：
文献类型：
--
作者：
Kubo, Fumi;Nakagawa, Shinichi
在脊椎动物视网膜中，干细胞样祖细胞维持在称为睫状边缘区（CMZ）的独特区域中。经典Wnt信号传导调节CMZ中祖细胞的维持。然而，其下游的分子机制仍不清楚。在这里，我们表明，鸡Hairy1，一个既定的Notch信号效应，介导的Wnt依赖的维持CMZ祖细胞在鸡。有趣的是，与Hes基因表达受Notch信号调节的其他发育环境不同，CMZ中的Hairy1表达受Wnt信号调节。Hairy1对于CMZ的一组分子标志物的表达是必要的和足够的，并且当Hairy1活性被抑制时，Wnt2b不能诱导CMZ标志物。此外，微阵列分析鉴定了多种激活Hairy1表达的Wnt响应性转录因子。因此，我们提出Hairy1作为Wnt信号传导的下游节点发挥作用，以维持鸡CMZ中的祖细胞。
In the vertebrate retina, stem cell-like progenitor cells are maintained in a distinct region called the ciliary marginal zone (CMZ). Canonical Wnt signaling regulates the maintenance of the progenitor cells in the CMZ. However, its downstream molecular mechanisms have remained largely unclear. Here, we show that chick Hairy1, an established Notch signaling effector, mediates the Wnt-dependent maintenance of CMZ progenitor cells in chicken. Interestingly, unlike other developmental contexts in which Hes gene expression is regulated by Notch signaling, Hairy1 expression in the CMZ is regulated by Wnt signaling. Hairy1 is necessary and sufficient for the expression of a set of molecular markers characteristic of the CMZ, and Wnt2b fails to induce CMZ markers when Hairy1 activity is inhibited. Furthermore, microarray analysis identifies multiple Wnt-responsive transcription factors that activate Hairy1 expression. We thus propose that Hairy1 functions as a node downstream of Wnt signaling to maintain progenitor cells in the chick CMZ.