Veien Eric S, Rosenthal Judith S, Kruse-Bend Renee C, Chien Chi-Bin, Dorsky Richard I
Department of Neurobiology and Anatomy, University of Utah, 401 MREB, 20 N. 1900 E., Salt Lake City, UT 84132, USA.
Development. 2008 Dec;135(24):4101-11. doi: 10.1242/dev.027367. Epub 2008 Nov 12.
Accurate retinotectal axon pathfinding depends upon the correct establishment of dorsal-ventral retinal polarity. We show that dorsal retinal gene expression is regulated by Wnt signaling in the dorsal retinal pigment epithelium (RPE). We find that a Wnt reporter transgene and Wnt pathway components are expressed in the dorsal RPE beginning at 14-16 hours post-fertilization. In the absence of Wnt signaling, tbx5 and Bmp genes initiate normal dorsal retinal expression but are not maintained. The expression of these genes is rescued by the downstream activation of Wnt signaling, and tbx5 is rescued by Bmp signaling. Furthermore, activation of Wnt signaling cannot rescue tbx5 in the absence of Bmp signaling, suggesting that Wnt signaling maintains dorsal retinal gene expression by regulating Bmp signaling. We present a model in which dorsal RPE-derived Wnt activity maintains the expression of Bmp ligands in the dorsal retina, thus coordinating the patterning of these two ocular tissues.
精确的视网膜-顶盖轴突寻路依赖于背-腹视网膜极性的正确建立。我们发现,背侧视网膜基因表达受背侧视网膜色素上皮(RPE)中Wnt信号通路调控。我们发现,一个Wnt报告基因转基因和Wnt信号通路成分在受精后14 - 16小时开始在背侧RPE中表达。在缺乏Wnt信号时,tbx5和Bmp基因开始正常的背侧视网膜表达,但不能维持。这些基因的表达通过Wnt信号通路的下游激活得以挽救,而tbx5通过Bmp信号通路得以挽救。此外,在缺乏Bmp信号时,Wnt信号通路的激活不能挽救tbx5,这表明Wnt信号通路通过调节Bmp信号通路来维持背侧视网膜基因表达。我们提出了一个模型,其中背侧RPE衍生的Wnt活性维持背侧视网膜中Bmp配体的表达,从而协调这两个眼组织的模式形成。