PAX6 is essential for neural retina (NR) and forebrain development but how PAX6 instructs NR versus forebrain specification remains unknown. We found that the paired‐less PAX6, PAX6D, is expressed in NR cells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells. hESCs deficient for PAX6D failed to enter NR specification. Induced expression of PAX6D but not PAX6A in a PAX6‐null background restored the NR specification capacity. ChIP‐Seq, confirmed by functional assays, revealed a set of retinal genes and non‐retinal neural genes that are potential targets of PAX6D, including WNT8B. Inhibition of WNTs or knocking down of WNT8B restored the NR specification capacity of neuroepithelia with PAX6D knockout, whereas activation of WNTs blocked NR specification even when PAX6D was induced. Thus, PAX6D specifies neuroepithelia to NR cells via the regulation of WNT8B.

中文翻译：

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PAX6D 指导人胚胎干细胞衍生的神经外胚层的神经视网膜规范。

PAX6 对神经视网膜 (NR) 和前脑发育至关重要，但 PAX6 如何指导 NR 与前脑规范仍然未知。我们发现无配对的 PAX6 PAX6D 在人眼发育过程中的 NR 细胞中表达，并沿着人胚胎干细胞 (hESC) 向视网膜细胞表达。缺乏 PAX6D 的 hESC 未能进入 NR 规范。在 PAX6-null 背景中诱导表达 PAX6D 而不是 PAX6A 恢复了 NR 规范容量。通过功能分析证实的 ChIP-Seq 揭示了一组作为 PAX6D 潜在靶标的视网膜基因和非视网膜神经基因，包括 WNT8B。WNT 的抑制或 WNT8B 的敲低恢复了 PAX6D 敲除的神经上皮的 NR 规范能力，而 WNT 的激活阻止了 NR 规范，即使在 PAX6D 被诱导时。因此，