Int J Biol Sci 2015; 11(6):688-700. doi:10.7150/ijbs.11244 This issue

Research Paper

Zebrafish Lbh-like Is Required for Otx2-mediated Photoreceptor Differentiation

Wen-Hua Li1,2, Li Zhou1✉, Zhi Li1, Yang Wang1, Jian-Tao Shi1, Yan-Jing Yang1,2, Jian-Fang Gui1 ✉

1. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences,
2. Graduate University of the Chinese Academy of Sciences, Wuhan 430072, China

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Li WH, Zhou L, Li Z, Wang Y, Shi JT, Yang YJ, Gui JF. Zebrafish Lbh-like Is Required for Otx2-mediated Photoreceptor Differentiation. Int J Biol Sci 2015; 11(6):688-700. doi:10.7150/ijbs.11244. Available from

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Graphic abstract

The homeobox transcription factor orthodenticle homolog 2 (otx2) is supposed as an organizer that orchestrates a transcription factor network during photoreceptor development. However, its regulation in the process remains unclear. In this study, we have identified a zebrafish limb bud and heart-like gene (lbh-like), which is expressed initially at 30 hours post fertilization (hpf) in the developing brain and eyes. Lbh-like knockdown by morpholinos specifically inhibits expression of multiple photoreceptor-specific genes, such as opsins, gnat1, gnat2 and irbp. Interestingly, otx2 expression in the morphants is not significantly reduced until 32 hpf when lbh-like begins to express, but its expression level in 72 hpf morphants is higher than that in wild type embryos. Co-injection of otx2 and its downstream target neuroD mRNAs can rescue the faults in eyes of Lbh-like morphants. Combined with the results of promoter-reporter assay, we suggest that lbh-like is a new regulator of photoreceptor differentiation directly through affecting otx2 expression in zebrafish. Furthermore, knockdown of lbh-like increases the activity of Notch pathway and perturbs the balance among proliferation, differentiation and survival of photoreceptor precursors.

Keywords: Lbh-like, retina development, photoreceptor differentiation, otx2, Notch