miR-132/212 modulates seasonal adaptation and dendritic morphology of the central circadian clock
HOT OFF THE PRESSES - The genetics of adjusting your internal clock to day length! PhD student Lucia Mendoz-Viveros (Cheng Lab) just yesterday published her 1st First Authored Paper. And this is a whopper of a paper in Cell Reports, entitled: “miR-132/212 modulates seasonal adaptation and dendritic morphology of the central circadian clock”. In this paper, Lucia examines the role of the microRNA gene cluster, miR-132/212, in circadian timekeeping using miR-132/212 knockout mice. She finds that genetic ablation of miR-132/212 alters the ability of mice to adjust their clock in response to varying day lengths. At the behavioural level, miR-132/212 knockout mice are better than wild-type animals at adapting to winter days, but have more difficulty adapting to summer days. This difference in seasonal adaptation is correlated with differences in the morphology of neurons in the master circadian pacemaker, the suprachiasmatic nucleus (SCN): miR-132/212 knockout mice have reduced dendritic spine density. Using Syrian hamsters (a model seasonal rodent), Lucia showed that day length not only regulates dendritic spine density in the SCN, but also affects the expression of miR-132, miR-212, their downstream target gene methyl CpG binding protein 2 (MeCP2) and its transcriptional target, brain-derived neurotrophic factor (BDNF). In a final set of experiments using MeCP2 knockout mice bred onto a miR-132/212 knockout background, Lucia showed that MeCP2 mediates the effects of miR-132/212 on dendritic spine density. Altogether, the data provide the first evidence that seasonal timekeeping by the SCN involves changes in dendritic morphology via a miR-132/212-MeCP2-dependent pathway. U
TM grad and undergrad coauthors on this paper include Jonathan Ong, Sara Hegazi, Arthur Cheng, Pascale Bouchard-Cannon, Michael Fana, Christopher Lowden, Peng Zhang, and Matthew Michiewicz.
Congratulations Lucia and Team Cheng!