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首页> 外文期刊>Molecular and Cellular Biology >Gbx2 Directly Restricts Otx2 Expression to Forebrain and Midbrain, Competing with Class III POU Factors
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Gbx2 Directly Restricts Otx2 Expression to Forebrain and Midbrain, Competing with Class III POU Factors

机译：Gbx2与III类POU因子竞争，直接将Otx2表达限制在前脑和中脑

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Otx2 plays essential roles in rostral brain development, and its counteraction with Gbx2 has been suggested to determine the midbrain-hindbrain boundary (MHB) in vertebrates. We previously identified the FM enhancer that is conserved among vertebrates and drives Otx2 transcription in forebrain/midbrain from the early somite stage. In this study, we found that the POU homeodomain of class III POU factors (Brn1, Brn2, Brn4, and Oct6) associates with noncanonical target sequence TAATTA in the FM enhancer. MicroRNA-mediated knockdown of Brn2 and Oct6 diminished the FM enhancer activity in anterior neural progenitor cells (NPCs) differentiated from P19 cells. The class III POU factors associate with the FM enhancer in forebrain and midbrain but not in hindbrain. We also demonstrated that the Gbx2 homeodomain recognizes the same target TAATTA in the FM enhancer, and Gbx2 associates with the FM enhancer in hindbrain. Gbx2 misexpression in the anterior NPCs repressed the FM enhancer activity and inhibited Brn2 association with the enhancer, whereas Gbx2 knockdown caused ectopic Brn2 association in the posterior NPCs. These results suggest that class III POU factors and Gbx2 share the same target site, TAATTA, in the FM enhancer and that their region-specific binding restricts Otx2 expression at the MHB.
机译： Otx2 在眼部大脑发育中起着至关重要的作用，它与 Gbx2 的相互作用被认为可以确定脊椎动物的中脑-后脑边界（MHB）。我们先前确定了FM增强子，该增强子在脊椎动物中很保守，并从早期步入早期开始在前脑/中脑中驱动 Otx2 转录。在这项研究中，我们发现III类POU因子（Brn1，Brn2，Brn4和Oct6）的POU同源域与FM增强子中的非常规靶序列TAATTA相关。 MicroRNA介导的敲低Brn2和Oct6减少了从P19细胞分化出的前神经祖细胞（NPC）中的FM增强子活性。 III类POU因子与前脑和中脑的FM增强剂有关，而与后脑无关。我们还证明了Gbx2同源域在FM增强子中识别相同的目标TAATTA，而Gbx2在后脑中与FM增强子相关。前鼻咽癌中的 Gbx2 表达异常抑制了FM增强子的活性并抑制了Brn2与增强子的缔合，而Gbx2的敲低导致后鼻咽癌中的异位Brn2缔合。这些结果表明，III类POU因子和Gbx2在FM增强子中具有相同的靶位点TAATTA，并且它们的区域特异性结合限制了MHB的 Otx2 表达。

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