PAX6D 从人胚胎干细胞衍生的神经外胚层指导神经视网膜特化。
PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm.
机构信息
Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Department of Rehabilitation of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
EMBO Rep. 2020 Sep 3;21(9):e50000. doi: 10.15252/embr.202050000. Epub 2020 Jul 23.
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.
PAX6 对于神经视网膜（NR）和前脑的发育至关重要，但 PAX6 如何指示 NR 与前脑的特化仍然未知。我们发现，配对缺失的 PAX6（PAX6D）在人类眼睛发育过程中以及沿着人类胚胎干细胞（hESC）特化到视网膜细胞的过程中在 NR 细胞中表达。PAX6D 缺陷的 hESC 未能进入 NR 特化。在 PAX6 缺失的背景下诱导表达 PAX6D 而不是 PAX6A 恢复了 NR 特化能力。ChIP-Seq 通过功能测定得到证实，揭示了一组视网膜基因和非视网膜神经基因，它们可能是 PAX6D 的靶标，包括 WNT8B。抑制 WNTs 或敲低 WNT8B 恢复了 PAX6D 缺失的神经上皮的 NR 特化能力，而激活 WNTs 甚至在诱导 PAX6D 时也阻止了 NR 特化。因此，PAX6D 通过调节 WNT8B 将神经上皮特化为 NR 细胞。
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