Heart neurons use clock genes to control myocyte proliferation

Authors: Emmanouil Tampakakis, Harshi Gangrade, Stephanie Glavaris, Myo Htet, Sean Murphy, Brian L. Lin, Ting Liu, Amir Saberi, Matthew Miyamoto, William J. Kowalski, Yoh‐suke Mukouyama, Gabsang Lee, Liliana Minichiello, Chulan Kwon - Science Advances 2021 cited by 39

deletion increased heart size and cardiomyocyte proliferation, recapitulating sympathetic neuron–deficient hearts. Conversely, increasing sympathetic activity by norepinephrine treatment induced Per1/Per2 and suppressed cardiomyocyte proliferation. We further found that the two clock genes negatively regulate myocyte mitosis entry through the Wee1 kinase pathway. Our findings demonstrate a previously unknown link between cardiac neurons and clock genes in regulation of cardiomyocyte proliferation and heart size and provide mechanistic insights for developing neuromodulation strategies for cardiac regen5eration.