title: Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction.
abstract: 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.
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bressan
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA.
authors.forename: PoAn Brian
authors.initials: PB
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Louie
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Navetta
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Garriock
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, 555 Mission Bay Boulevard South, San Francisco, CA 94143-3120, USA takashi.mikawa@ucsf.edu.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mikawa
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D002642:Chick Embryo; D004699:Endocardium / Q000166:cytology* / Q000378:metabolism; D006321:Heart / Q000196:embryology; D017403:In Situ Hybridization; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism
keywords: Action potential; Atrioventricular junction; Conduction velocity diversification; Heart patterning; Optical mapping