The Drosophila Wilms׳ Tumor 1-Associating Protein (WTAP) homolog is required for eye development.
The Drosophila Wilms׳ Tumor 1-Associating Protein (WTAP) homolog is required for eye development.
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DOI：
10.1016/j.ydbio.2014.03.012
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发表时间：
2014-06-15
影响因子：
2.7
通讯作者：
Kumar, Justin R.
中科院分区：
文献类型：
--
作者：
Anderson, Abigail M.;Weasner, Brandon P.;Weasner, Bonnie M.;Kumar, Justin R.
Sine Oculis(Sine Oculis，Sine Oculis)是六个同源框转录因子家族的创始成员，它与特定的DNA元件结合，调节下游靶基因的转录。这在一定程度上是通过形成不同的生物化学复合体来实现的，没有眼睛(Eya)和Groucho(Gro)。虽然这些复合体在发育过程中发挥着重要作用，但它们并不能解释果蝇中所有依赖于SO的活动。人们认为，更多的含硫络合物也有重要的贡献。这一论点得到了近24种与SO复合的额外蛋白质的鉴定的支持。然而，人们对这些额外的复合体在发育中所起的作用知之甚少。在这份报告中，我们使用酵母双杂交筛选和免疫共沉淀试验从Kc167细胞中鉴定了一个由SO和人类Wilms肿瘤相关蛋白(WTAP)的果蝇同源物Fl(2)d组成的生化复合体。我们发现，Fl(2)d蛋白分布于整个眼-触角成像盘，功能丧失突变导致视网膜发育紊乱。眼睛缺陷表现在形态发生皱纹后面，部分原因是泛神经元RNA结合蛋白、胚胎致死性异常视觉(ELAV)和RUNX类转录因子Lozenger(LZ)水平升高。我们还提供了So和Fl(2)d在发育中的眼睛中存在遗传相互作用的证据。Wilms‘s Tumor-1(WT1)是WTAP的结合伙伴，是哺乳动物正常眼睛形成所必需的，功能丧失突变与某些版本的视网膜母细胞瘤有关。相比之下，WTAP及其同系物并未与眼睛发育有关。据我们所知，这份报告中提出的结果是第一次描述WTAP在任何有视力的动物的视网膜中的作用。
Sine Oculis (So), the founding member of the SIX family of homeobox transcription factors, binds to sequence specific DNA elements and regulates transcription of downstream target genes. It does so, in part, through the formation of distinct biochemical complexes with Eyes Absent (Eya) and Groucho (Gro). While these complexes play significant roles during development, they do not account for all So-dependent activities in Drosophila. It is thought that additional So-containing complexes make important contributions as well. This contention is supported by the identification of nearly two-dozen additional proteins that complex with So. However, very little is known about the roles that these additional complexes play in development. In this report we have used yeast two-hybrid screens and co-immunoprecipitation assays from Kc167 cells to identify a biochemical complex consisting of So and Fl(2)d, the Drosophila homolog of human Wilms’ Tumor 1-Associating Protein (WTAP). We show that Fl(2)d protein is distributed throughout the entire eye-antennal imaginal disc and that loss-of-function mutations lead to perturbations in retinal development. The eye defects are manifested behind the morphogenetic furrow and result in part from increased levels of the pan-neuronal RNA binding protein Embryonic Lethal Abnormal Vision (Elav) and the RUNX class transcription factor Lozenge (Lz). We also provide evidence that So and Fl(2)d interact genetically in the developing eye. Wilms’ tumor-1 (WT1), a binding partner of WTAP, is required for normal eye formation in mammals and loss-of-function mutations are associated with some versions of retinoblastoma. In contrast, WTAP and its homologs have not been implicated in eye development. To our knowledge, the results presented in this report are the first description of a role for WTAP in the retina of any seeing animal.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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发表时间：
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