Deficiency of the clock gene Bmal1 affects neural progenitor cell migration.

We demonstrate the impact of a disrupted molecular clock in Bmal1-deficient (Bmal1) mice on migration of neural progenitor cells (NPCs). Proliferation of NPCs in rostral migratory stream (RMS) was reduced in Bmal1 mice, consistent with our earlier studies on adult neurogenesis in hippocampus. However, a significantly higher number of NPCs from Bmal1 mice reached the olfactory bulb as compared to wild-type littermates (Bmal1 mice), indicating a higher migration velocity in Bmal1 mice. In isolated NPCs from Bmal1 mice, not only migration velocity and expression pattern of genes involved in detoxification of reactive oxygen species were affected, but also RNA oxidation of catalase was increased and catalase protein levels were decreased. Bmal1 migration phenotype could be restored by treatment with catalase, while treatment of NPCs from Bmal1 mice with hydrogen peroxide mimicked Bmal1 migration phenotype. Thus, we conclude that Bmal1 deficiency affects NPC migration as a consequence of dysregulated detoxification of reactive oxygen species.