Basinski Brian W, Huang Yuanhao, Li Qiang, Sivakumar Charukesi D, Carman Tyler J, Pan Hana M, Xu Jing, Hannum D Ford, Liu Jie, Rao Rajesh C
Department of Ophthalmology and Visual Science, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA; Molecular and Cellular Pathology Graduate Program, Department of Pathology, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Ophthalmology and Visual Science, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA; Department of Computational Medicine and Bioinformatics, Ann Arbor, MI 48105, USA.
Stem Cell Reports. 2025 Jun 10;20(6):102508. doi: 10.1016/j.stemcr.2025.102508. Epub 2025 May 22.
The transcriptional regulation underlying eye field (retinal primordium) development requires precise control, yet the mechanisms guiding lineage-specific differentiation within the central nervous system (CNS) remain incompletely understood. Using neuroectoderm (NE) organoids derived from mouse embryonic stem cells, we investigate the role of PRDM13 in eye field specification. We demonstrate that Prdm13 expression inhibits RX eye field fate but permits non-eye field NE differentiation, an effect that depends on its first and second zinc-finger domains. Prdm13 activates the WNT/β-catenin signaling pathway during differentiation, leading to downregulation of key transcription factors crucial for establishing the eye field. Pharmacological inhibition of WNT signaling abolishes PRDM13-mediated suppression, restoring RX eye field differentiation. Our work reveals a previously undescribed PRDM13-WNT signaling axis that regulates lineage-specific neural differentiation of embryonic stem cells.
眼场（视网膜原基）发育的转录调控需要精确控制，但指导中枢神经系统（CNS）内谱系特异性分化的机制仍未完全了解。利用从小鼠胚胎干细胞衍生的神经外胚层（NE）类器官，我们研究了PRDM13在眼场特化中的作用。我们证明，Prdm13表达抑制RX眼场命运，但允许非眼场NE分化，这一效应取决于其第一和第二个锌指结构域。Prdm13在分化过程中激活WNT/β-连环蛋白信号通路，导致对建立眼场至关重要的关键转录因子下调。WNT信号的药理学抑制消除了PRDM13介导的抑制作用，恢复了RX眼场分化。我们的工作揭示了一个以前未描述的PRDM13-WNT信号轴，该信号轴调节胚胎干细胞的谱系特异性神经分化。
