title: Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart.
abstract: Impulse-conducting Purkinje fibers differentiate from myocytes during embryogenesis. The conversion of contractile myocytes into conduction cells is induced by the stretch/pressure-induced factor, endothelin (ET). Active ET is produced via proteolytic processing from its precursor by ET-converting enzyme 1 (ECE1) and triggers signaling by binding to its receptors. In the embryonic chick heart, ET receptors are expressed by all myocytes, but ECE1 is predominantly expressed in endothelial cells of coronary arteries and endocardium along which Purkinje fiber recruitment from myocytes takes place. Furthermore, co-expression of exogenous ECE1 and ET-precursor in the embryonic heart is sufficient to ectopically convert cardiomyocytes into Purkinje fibers. Thus, localized expression of ECE1 defines the site of Purkinje fiber recruitment in embryonic myocardium. However, it is not known how ECE1 expression is regulated in the embryonic heart. The unique expression pattern of ECE1 in the embryonic heart suggests that blood flow-induced stress/stretch may play a role in patterning ECE1 expression and subsequent induction of Purkinje fiber differentiation. We show that gadolinium, an antagonist for stretch-activated cation channels, downregulates the expression of ECE1 and a conduction cell marker, Cx40, in ventricular chambers, concurrently with delayed maturation of a ventricular conduction pathway. Conversely, pressure-overload in the ventricle by conotruncal banding results in a significant expansion of endocardial ECE1 expression and Cx40-positive putative Purkinje fibers. Coincident with this, an excitation pattern typical of the mature heart is precociously established. These in vivo data suggest that biomechanical forces acting on, and created by, the cardiovascular system during embryogenesis play a crucial role in Purkinje fiber induction and patterning.
authors.affiliation: Department of Cell and Developmental Biology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Hall
authors.forename: Romulo
authors.initials: R
authors.lastname: Hurtado
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Hewett
authors.forename: Maxim
authors.initials: M
authors.lastname: Shulimovich
authors.forename: Clifton P
authors.initials: CP
authors.lastname: Poma
authors.forename: Maria
authors.initials: M
authors.lastname: Reckova
authors.forename: Chip
authors.initials: C
authors.lastname: Justus
authors.forename: David J
authors.initials: DJ
authors.lastname: Pennisi
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gourdie
authors.forename: Takashi
authors.initials: T
authors.lastname: Mikawa
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D015536:Down-Regulation / Q000502:physiology; D000072396:Endothelin-Converting Enzymes; D005682:Gadolinium / Q000378:metabolism; D006321:Heart / Q000196:embryology* / Q000502:physiology; D008666:Metalloendopeptidases; D011690:Purkinje Fibers / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005682:Gadolinium; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes