Abstract
It has been suggested that Jmjd6 plays an important role in gene regulation through its demethylation or hydroxylation activity on histone and transcription factors. In addition, Jmjd6 has been shown to regulate RNA splicing by interaction with splicing factors. In this study, we demonstrated that Jmjd6a is expressed in developing Xenopus laevis eye during optic vesicle formation and retinal layer differentiation stages. Knockdown of Jmjd6a by an antisense morpholino resulted in eye malformation including a deformed retinal layer and no lens formation. We further found down-regulation of gene expression related to eye development such as Rx1, Otx2, and Pax6 in Jmjd6a morpholino injected embryos. Jmjd6 interacts with splicing factor U2AF25 and GSK3β RNA in the anterior region of Xenopus embryos. Knockdown of Jmjd6a led to deletion of GSK3β RNA exon 1 and 2, which resulted in generation of N’-terminal truncated GSK3β protein. This event further caused decreased phosphorylation of β-catenin and subsequently increased β-catenin stability. Therefore, our result may suggest that Jmjd6a plays an important role in Xenopus eye development through regulation of GSK3β RNA splicing and canonical Wnt/β-catenin signaling.
Highlights
During vertebrate eye development, spatiotemporal orchestration of eye-specific gene expression occurs between different cell types from different embryonic origins including the neural ectoderm, surface ectoderm, and periocular mesenchyme [1]
We demonstrated that Jmjd6a is expressed in developing Xenopus laevis eye during optic vesicle formation and retinal layer differentiation stages
It has been reported that mammalian Jmjd6 regulates gene expression by modification of histones or transcription factors [13, 18, 39]
Summary
Spatiotemporal orchestration of eye-specific gene expression occurs between different cell types from different embryonic origins including the neural ectoderm, surface ectoderm, and periocular mesenchyme [1]. Muller glial cells span all retinal layers These developmental events are tightly regulated by signaling cascades, which control cellular proliferation and differentiation [1]. In the absence of Wnt, β-catenin is phosphorylated at Thr 41, Ser 33, Ser 37, and Thr 41 by GSK3β, which is a member of the β-catenin destruction complex composed of multiple proteins including APC, axin, and CK1α This subsequently triggers β-catenin destabilization by ubiquitination [7, 8]. Knockdown of Jmjd6a by antisense morpholino led to augmented canonical Wnt/β-catenin signaling through generation of aberrant GSK3β RNA, which resulted in the production of N-terminal truncated GSK3β protein. These events may cause abnormal eye development in Xenopus embryos
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