Chow R L, Altmann C R, Lang R A, Hemmati-Brivanlou A
Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016, USA.
Development. 1999 Oct;126(19):4213-22. doi: 10.1242/dev.126.19.4213.
We report here that misexpression of the transcription factor Pax6 in the vertebrate Xenopus laevis leads to the formation of differentiated ectopic eyes. Multiple molecular markers indicated the presence of mature lens fiber cells, ganglion cells, Müller cells, photoreceptors and retinal pigment epithelial cells in a spatial arrangement similar to that of endogenous eyes. Lineage tracing experiments showed that lens, retina and retinal pigment epithelium arose as a consequence of the cell-autonomous function of Pax6. These experiments also reveal that the cell autonomous activity of misexpressed Pax6 causes the ectopic expression of a number of genes including Rx, Otx2, Six3 and endogenous Pax6, each of which has been implicated in eye development. The formation of ectopic and endogenous eyes could be suppressed by coexpression of a dominant-negative form of Pax6. These data show that in vertebrates, as in the invertebrate Drosophila melanogaster, Pax6 is both necessary and sufficient to trigger the cascade of events required for eye formation.
我们在此报告，转录因子Pax6在脊椎动物非洲爪蟾中的错误表达会导致分化的异位眼形成。多种分子标记表明，存在成熟的晶状体纤维细胞、神经节细胞、米勒细胞、光感受器和视网膜色素上皮细胞，其空间排列类似于内源性眼睛。谱系追踪实验表明，晶状体、视网膜和视网膜色素上皮的出现是Pax6细胞自主功能的结果。这些实验还揭示，错误表达的Pax6的细胞自主活性会导致包括Rx、Otx2、Six3和内源性Pax6在内的许多基因的异位表达，其中每个基因都与眼睛发育有关。通过共表达显性负性形式的Pax6可以抑制异位眼和内源性眼的形成。这些数据表明，在脊椎动物中，与无脊椎动物黑腹果蝇一样，Pax6对于触发眼睛形成所需的一系列事件既是必要的也是充分的。
