ハットリ　フミユキ   HATTORI FUMIYUKI   服部　文幸    所属   関西医科大学  iPS・幹細胞再生医学講座    職種   研究教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	Sema3a maintains normal heart rhythm through sympathetic innervation patterning.
掲載誌名	正式名：Nature medicine 略　 称：Nat Med ISSNコード：1078895610788956
巻・号・頁	13(5),pp.604-12
著者・共著者	Ieda Masaki, Kanazawa Hideaki, Kimura Kensuke, Hattori Fumiyuki, Ieda Yasuyo, Taniguchi Masahiko, Lee Jong-Kook, Matsumura Keisuke, Tomita Yuichi, Miyoshi Shunichiro, Shimoda Kouji, Makino Shinji, Sano Motoaki, Kodama Itsuo, Ogawa Satoshi, Fukuda Keiichi
発行年月	2007/05
概要	Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a, establishes cardiac sympathetic innervation patterning. Sema3a is abundantly expressed in the trabecular layer in early-stage embryos but is restricted to Purkinje fibers after birth, forming an epicardial-to-endocardial transmural sympathetic innervation patterning. Sema3a(-/-) mice lacked a cardiac sympathetic innervation gradient and exhibited stellate ganglia malformation, which led to marked sinus bradycardia due to sympathetic dysfunction. Cardiac-specific overexpression of Sema3a in transgenic mice (SemaTG) was associated with reduced sympathetic innervation and attenuation of the epicardial-to-endocardial innervation gradient. SemaTG mice demonstrated sudden death and susceptibility to ventricular tachycardia, due to catecholamine supersensitivity and prolongation of the action potential duration. We conclude that appropriate cardiac Sema3a expression is needed for sympathetic innervation patterning and is critical for heart rate control.
DOI	10.1038/nm1570
PMID	17417650