The molecular events driving specification of the kidney have been well characterized. However, how the initial kidney field size is established, patterned, and proportioned is not well characterized. Lhx1 is a transcription factor expressed in pronephric progenitors and is required for specification of the kidney, but few Lhx1 interacting proteins or downstream targets have been identified. By tandem-affinity purification, we isolated FRY like transcriptional coactivator (Fryl), one of two paralogous genes, fryl and furry (fry), have been described in vertebrates. Both proteins were found to interact with the Ldb1-Lhx1 complex, but our studies focused on Lhx1/Fry functional roles, as they are expressed in overlapping domains. We found that Xenopus embryos depleted of fry exhibit loss of pronephric mesoderm, phenocopying the Lhx1-depleted animals. In addition, we demonstrated a synergism between Fry and Lhx1, identified candidate microRNAs regulated by the pair, and confirmed these microRNA clusters influence specification of the kidney. Therefore, our data shows that a constitutively-active Ldb1-Lhx1 complex interacts with a broadly expressed microRNA repressor, Fry, to establish the kidney field.

中文翻译：

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Lhx1-Ldb1复合物与毛茸茸相互作用，以调节肾前肾发育过程中的microRNA表达。

肾脏活动的分子事件已得到很好的表征。但是，如何确定，构图和按比例分配初始肾脏视野大小并没有很好的特征。Lhx1是在前肾祖细胞中表达的转录因子，是肾脏规格所必需的，但是几乎没有Lhx1相互作用蛋白或下游靶标被鉴定出来。通过串联亲和纯化，我们分离了FRY，如转录共激活因子（Fryl），这是两个旁系同源基因fryl和furry（fry）之一，已在脊椎动物中进行了描述。发现这两种蛋白都与Ldb1-Lhx1复合体相互作用，但是我们的研究集中在Lhx1 / Fry功能上，因为它们在重叠结构域中表达。我们发现，耗尽鱼苗的非洲爪蟾胚胎表现出前肾中胚层的丧失，表型显示Lhx1耗尽的动物。此外，我们证明了Fry和Lhx1之间的协同作用，鉴定了受该对调节的候选microRNA，并证实了这些microRNA簇影响肾脏的规格。因此，我们的数据表明，具有组成型活性的Ldb1-Lhx1复合物与广泛表达的microRNA阻遏物Fry相互作用，以建立肾脏视野。