Heart neurons use clock genes to control myocyte proliferation
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
Abstract
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.