Takahashi Hiroo, Shintani Takafumi, Sakuta Hiraki, Noda Masaharu
Division of Molecular Neurobiology, National Institute for Basic Biology, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
Development. 2003 Nov;130(21):5203-15. doi: 10.1242/dev.00724. Epub 2003 Sep 3.
Chick brain factor 1 (CBF1), a nasal retina-specific winged-helix transcription factor, is known to prescribe the nasal specificity that leads to the formation of the precise retinotectal map, especially along the anteroposterior (AP) axis. However, its downstream topographic genes and the molecular mechanisms by which CBF1 controls the expression of them have not been elucidated. We show that misexpression of CBF1 represses the expression of EphA3 and CBF2, and induces that of SOHo1, GH6, ephrin A2 and ephrin A5. CBF1 controls ephrin A5 by a DNA binding-dependent mechanism, ephrin A2 by a DNA binding-independent mechanism, and CBF2, SOHo1, GH6 and EphA3 by dual mechanisms. BMP2 expression begins double-gradiently in the retina from E5 in a complementary pattern to Ventroptin expression. Ventroptin antagonizes BMP2 as well as BMP4. CBF1 interferes in BMP2 signaling and thereby induces expression of ephrin A2. Our data suggest that CBF1 is located at the top of the gene cascade for the regional specification along the nasotemporal (NT) axis in the retina and distinct BMP signals play pivotal roles in the topographic projection along both axes.
鸡脑因子1（CBF1）是一种鼻视网膜特异性的翼状螺旋转录因子，已知它决定了导致精确视网膜顶盖图谱形成的鼻特异性，特别是沿着前后（AP）轴。然而，其下游的拓扑基因以及CBF1控制它们表达的分子机制尚未阐明。我们发现，CBF1的错误表达会抑制EphA3和CBF2的表达，并诱导SOHo1、GH6、ephrin A2和ephrin A5的表达。CBF1通过依赖DNA结合的机制控制ephrin A5，通过不依赖DNA结合的机制控制ephrin A2，并通过双重机制控制CBF2、SOHo1、GH6和EphA3。从E5期开始，BMP2在视网膜中的表达呈双梯度，与Ventroptin的表达呈互补模式。Ventroptin拮抗BMP2以及BMP4。CBF1干扰BMP2信号传导，从而诱导ephrin A2的表达。我们的数据表明，CBF1位于视网膜沿鼻颞（NT）轴区域特异性基因级联的顶端，不同的BMP信号在沿两个轴的拓扑投射中起关键作用。
