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Cell Rep 2022 Feb 01;385:110312. doi: 10.1016/j.celrep.2022.110312.
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Zic5 stabilizes Gli3 via a non-transcriptional mechanism during retinal development.

Sun J , Yoon J , Lee M , Lee HK , Hwang YS , Daar IO .

The Zic family of zinc finger transcription factors plays a critical role 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.

PubMed ID: 35108539
PMC ID: PMC8843030
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ccnd1 gli1 gli2 gli3 hes1 hes5 hes5.2 isl1 isyna1 mitf otx2 pax6 ptch1 rax rho rpe rpe65 shh tp53 zic5
Antibodies: Casp3 Ab1 FLAG-HRP Ab1 GFP Ab24 Gli2 Ab3 Gli3 Ab1 HA Ab55 Isl1/2 Ab1 Myc Ab21 Pax6 Ab3 RPE65 Ab2 Rho Ab1 Zic5 Ab1
Morpholinos: gli3 MO1 zic5 MO1

Article Images: [+] show captions
References [+] :
Anderson, Fgf4 maintains Hes7 levels critical for normal somite segmentation clock function. 2020, Pubmed