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首页> 外文期刊>Molecular and Cellular Biology >Gbx2 and Otx2 Interact with the WD40 Domain of Groucho/Tle Corepressors
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Gbx2 and Otx2 Interact with the WD40 Domain of Groucho/Tle Corepressors

机译：Gbx2和Otx2与Groucho / Tle Corepressors的WD40域交互

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One of the earliest organizational decisions in the development of the vertebrate brain is the division of the neural plate into Otx2-positive anterior and Gbx2-positive posterior territories. At the junction of these two expression domains, a local signaling center is formed, known as the midbrain-hindbrain boundary (MHB). This tissue coordinates or “organizes” the development of neighboring brain structures, such as the midbrain and cerebellum. Correct positioning of the MHB is thought to depend on mutual repression involving these two homeobox genes. Using a cell culture colocalization assay and coimmunoprecipitation experiments, we show that engrailed homology region 1 (eh1)-like motifs of both transcription factors physically interact with the WD40 domain of Groucho/Tle corepressor proteins. In addition, heat shock-induced expression of wild-type and mutant Otx2 and Gbx2 in medaka embryos demonstrates that Groucho is required for the repression of Otx2 by Gbx2. On the other hand, the repressive functions of Otx2 on Gbx2 do not appear to be dependent on corepressor interaction. Interestingly, the association of Groucho with Otx2 is also required for the repression of Fgf8 in the MHB. Therefore Groucho/Tle family members appear to regulate key aspects in the MHB development of the vertebrate brain.
机译：脊椎动物大脑发育的最早组织决策之一是将神经板分为 Otx2 阳性前区和 Gbx2 阳性后区。在这两个表达域的交界处，形成了一个局部信号中心，称为中脑-后脑边界（MHB）。该组织协调或“组织”邻近大脑结构（例如中脑和小脑）的发育。 MHB的正确定位被认为取决于涉及这两个同源盒基因的相互抑制。使用细胞培养共定位测定和免疫共沉淀实验，我们表明，两个转录因子的同源性区域1（eh1）样基序都与Groucho / Tle抑癌蛋白的WD40域发生了物理相互作用。此外，热激诱导的青aka胚胎中野生型和突变型 Otx2 和 Gbx2 的表达表明，Groucho是抑制 Otx2 通过Gbx2。另一方面，Otx2对 Gbx2 的抑制功能似乎不依赖于corepressor相互作用。有趣的是，对于MHB中的 Fgf8 的抑制，还需要Groucho与Otx2的关联。因此，Groucho / Tle家族成员似乎在调节脊椎动物大脑MHB发育的关键方面。

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