Zic5 stabilizes Gli3 via a non-transcriptional mechanism during retinal development.
Zic5 stabilizes Gli3 via a non-transcriptional mechanism during retinal development.
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DOI：
10.1016/j.celrep.2022.110312
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发表时间：
2022-02-01
期刊：
影响因子：
8.8
通讯作者：
Daar IO
中科院分区：
文献类型：
--
作者：
Sun J;Yoon J;Lee M;Lee HK;Hwang YS;Daar IO
The Zic family of zinc finger transcription factors play critical roles in multiple developmental processes. Using loss of function studies, we find that Zic5 is important for the differentiation of Retinal Pigmented Epithelium (RPE) and the rod photoreceptor layer through suppressing Hedgehog (Hh) signaling. Further, Zic5 interacts with the critical Hh signaling molecule, Gli3, through the zinc finger domains of both proteins. This Zic5/Gli3 interaction disrupts Gli3/Gli3 homodimerization, resulting in Gli3 protein stabilization via a reduction in Gli3 ubiquitination. During embryonic Hh signaling, the activator form of Gli is normally converted to a repressor form through proteosome-mediated processing of Gli3, and the ratio of Gli3 repressor to full length (activator) form of Gli3 determines the Gli3 repressor output required for normal eye development. Our results suggest Zic5 is a critical player in regulating Gli3 stability for the proper differentiation of RPE and rod photoreceptor layer during Xenopus eye development. Sun et al. reveal a critical role for Zic5 in regulating the differentiation of retinal pigmented epithelium (RPE) and rod photoreceptor layer by interacting and stabilizing Gli3, which functions predominantly as a repressor for the Hedgehog (Hh) signaling pathway during Xenopus development.
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