title: Myocardialization of the cardiac outflow tract.
abstract: During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally, (vi) ventricular myocardium did not produce factors capable of supporting myocardialization.
authors.affiliation: Department of Anatomy and Embryology, Academic Medical Center, Meibergdreef 15, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: van den Hoff
authors.forename: A F
authors.initials: AF
authors.lastname: Moorman
authors.forename: J M
authors.initials: JM
authors.lastname: Ruijter
authors.forename: W H
authors.initials: WH
authors.lastname: Lamers
authors.forename: R W
authors.initials: RW
authors.lastname: Bennington
authors.forename: R R
authors.initials: RR
authors.lastname: Markwald
authors.forename: A
authors.initials: A
authors.lastname: Wessels
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002642:Chick Embryo; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D004627:Embryonic Induction; D006321:Heart / Q000196:embryology*; D006325:Heart Atria / Q000196:embryology; D006346:Heart Septum / Q000196:embryology; D006352:Heart Ventricles / Q000196:embryology; D008648:Mesoderm; D008961:Models, Structural; D009206:Myocardium / Q000166:cytology; D009924:Organ Culture Techniques
chemical_list: D017077:Culture Media, Conditioned