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