Midkine expression is regulated by the circadian clock in the retina of the zebrafish.

The retina displays numerous processes that follow a circadian rhythm. These processes are coordinated through the direct action of light on photoreceptive molecules and, in the absence of light, through autocrine/paracrine actions of extracellular neuromodulators. We previously described the expression of the genes encoding the secreted heparin-binding growth factors, midkine-a (mdka) and midkine-b (mdkb), in the retina of the zebrafish. Here, we provide evidence that the expression of mdka and mdkb follows a daily rhythm, which is independent of the presence or absence of light, and we propose that the expression of mdka is regulated by the circadian clock. Both qualitative and quantitative measures show that for mdka, the levels of mRNA and protein decrease during the night and increase during the subjective day. Qualitative measures show that the expression of mdkb increases during the second half of the subjective night and decreases during the second half of the subjective day. Within horizontal cells, the two midkine paralogs show asynchronous circadian regulation. Though intensely studied in the contexts of physiology and disease, this is the first study to provide evidence for the circadian regulation of midkines in the vertebrate nervous system.