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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.

Jmjd6a regulates GSK3β RNA splicing in Xenopus laevis eye development