RA (retinoic acid) signaling is essential for the patterning the hindbrain of vertebrates. Although hundreds of potential RA targets genes are identified, the ones other than hox genes playing roles in patterning anterior-posterior axis of hindbrain by mediating RA signaling remains largely unknown. Previously, we reported that znfl1s play essential roles in the formation of posterior neuroectoderm in zebrafish embryos. Here, we revealed that znfl1s play a critical role in patterning the posterior axis of hindbrain by maintaining the homeostasis of RA signaling in zebrafish embryos. Knocking down znfl1s shortened the length of the posterior hindbrain in a similar way of reducing RA signaling in zebrafish embryos and the defective posterior hindbrain was effectively rescued by elevating RA signaling. By performing mutagenesis assays and chromatin immunoprecipitation assays on the promoter of znfl1s, we demonstrated that znfl1s are direct target genes of RA to mediate RA signaling through a functional DR1 RA response element. Taken together, our results showed that Znfl1s are essential for patterning the anterior-posterior axis development of posterior hindbrain by acting as direct target genes of RA signaling.

中文翻译：

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Znfl1s 作为视黄酸的直接靶基因，对斑马鱼后脑的前后轴形成模式至关重要

RA（视黄酸）信号对于脊椎动物的后脑图案化至关重要。尽管已鉴定出数百个潜在的 RA 靶基因，但除了通过介导 RA 信号传导在后脑前后轴模式中发挥作用的 hox 基因之外的基因仍然很大程度上未知。以前，我们报道 znfl1s 在斑马鱼胚胎后神经外胚层的形成中起重要作用。在这里，我们揭示了 znfl1s 通过维持斑马鱼胚胎中 RA 信号传导的稳态，在后脑后轴的模式化中发挥关键作用。敲除 znfl1s 以减少斑马鱼胚胎中 RA 信号的类似方式缩短了后脑的长度，并且通过提高 RA 信号有效地挽救了有缺陷的后脑。通过对 znfl1s 的启动子进行诱变测定和染色质免疫沉淀测定，我们证明 znfl1s 是 RA 的直接靶基因，可通过功能性 DR1 RA 反应元件介导 RA 信号传导。总之，我们的结果表明，Znfl1s 通过充当 RA 信号传导的直接靶基因，对后脑的前后轴发育模式化至关重要。