期刊
DEVELOPMENT
卷 141, 期 21, 页码 4149-4157出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.110007
关键词
Action potential; Atrioventricular junction; Conduction velocity diversification; Heart patterning; Optical mapping
资金
- National Institutes of Health [1K99HL122360, T32 HD 007470, R01 HL093566, R01 HL112268, R01 HL078921]
Efficient blood flow depends on two developmental processes that occur within the atrioventricular junction (AVJ) of the heart: conduction delay, which entrains sequential chamber contraction; and valve formation, which prevents retrograde fluid movement. Defects in either result in severe congenital heart disease; however, little is known about the interplay between these two crucial developmental processes. Here, we show that AVJ conduction delay is locally assigned by the morphogenetic events that initiate valve formation. Our data demonstrate that physical separation from endocardial-derived factors prevents AVJ myocardium from becoming fast conducting. Mechanistically, this physical separation is induced by myocardial-derived factors that support cardiac jelly deposition at the onset of valve formation. These data offer a novel paradigm for conduction patterning, whereby reciprocal myocardial-endocardial interactions coordinate the processes of valve formation with establishment of conduction delay. This, in turn, synchronizes the electrophysiological and structural events necessary for the optimization of blood flow through the developing heart.
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