RAD21缺陷通过上调WNT9B驱动角膜向巩膜分化命运转换。
RAD21 deficiency drives corneal to scleral differentiation fate switching via upregulating WNT9B.
作者信息
Liu Hongyan, Qi Benxiang, Liu Guanghui, Duan Haoyun, Li Zongyi, Shi Zhaoying, Chen Yonglong, Chu Wai Kit, Zhou Qingjun, Zhang Bi Ning
机构信息
Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
出版信息
iScience. 2024 May 3;27(6):109875. doi: 10.1016/j.isci.2024.109875. eCollection 2024 Jun 21.
The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary between the cornea and sclera. Previously, we identified a mutation in a sclerocornea pedigree. Here, we investigated the impacts of on NCC activities during eye development. deficiency caused upregulation of . Both knockdown and upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that had 190.9-fold higher expression in scleral stroma than in corneal stroma. was also significantly upregulated by both knockdown and overexpression, and knock down of rescued the differentiation and migration of NCCs with deficiency. Consistently, overexpressing in led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression.
角膜和巩膜是相邻的不同组织，但其基质细胞起源于共同的神经嵴细胞（NCCs）。巩膜化角膜是一种以角膜和巩膜之间边界难以区分的疾病。此前，我们在一个巩膜化角膜家系中鉴定出一个突变。在此，我们研究了其对眼睛发育过程中NCC活动的影响。 缺乏导致 上调。 敲低和 上调均破坏了NCCs的迁移。转录组分析表明， 在巩膜基质中的表达比在角膜基质中高190.9倍。 也因 敲低和 过表达而显著上调，敲低 可挽救 缺乏时NCCs的分化和迁移。一致地，在 中过表达 会导致眼部发育异常。总之，WNT9B是NCC分化为角膜角质形成细胞或巩膜基质细胞过程中的一个决定性因素，并受RAD21表达的影响。
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