Shiraki Taisei, Hayashi Takuma, Ozue Jotaro, Watanabe Minoru
Graduate School of Sciences and Technology for Innovation, Tokushima University, 1-1 Minamijosanjima-Cho, Tokushima 770-8054, Japan.
Institute of Liberal Arts and Sciences, Tokushima University, 1-1 Minamijosanjima-Cho, Tokushima 770-8054, Japan.
J Dev Biol. 2022 Oct 29;10(4):46. doi: 10.3390/jdb10040046.
The Wilms' tumor suppressor gene, , encodes a zinc finger-containing transcription factor that binds to a GC-rich motif and regulates the transcription of target genes. was first identified as a tumor suppressor gene in Wilms' tumor, a pediatric kidney tumor, and has been implicated in normal kidney development. The WT1 protein has transcriptional activation and repression domains and acts as a transcriptional activator or repressor, depending on the target gene and context. In , an ortholog of has been isolated and shown to be expressed in the developing embryonic pronephros. To investigate the role of in pronephros development in embryos, we mutated by CRISPR/Cas9 and found that the expression of pronephros marker genes was reduced. In reporter assays in which known WT1 binding sequences were placed upstream of the gene, WT1 activated transcription of the gene. The injection of wild-type or artificially altered transcriptional activity of mRNA disrupted the expression of pronephros marker genes in the embryos. These results suggest that the appropriate amounts and activity of WT1 protein are required for normal pronephros development in embryos.
威尔姆斯肿瘤抑制基因 ，编码一种含锌指结构的转录因子，该因子可与富含GC的基序结合并调节靶基因的转录。 最初被鉴定为小儿肾肿瘤威尔姆斯肿瘤中的肿瘤抑制基因，并与正常肾脏发育有关。WT1蛋白具有转录激活和抑制结构域，并根据靶基因和环境充当转录激活剂或抑制剂。在 中，已分离出 的直系同源基因，并显示其在发育中的胚胎前肾中表达。为了研究 在 胚胎前肾发育中的作用，我们通过CRISPR/Cas9对 进行了突变，发现前肾标记基因的表达降低。在将已知WT1结合序列置于 基因上游的报告基因分析中，WT1激活了 基因的转录。注射野生型或人工改变转录活性的 mRNA会破坏 胚胎中前肾标记基因的表达。这些结果表明， 胚胎正常前肾发育需要适量的WT1蛋白和活性。
