title: Conotruncal myocardium arises from a secondary heart field.
abstract: The primary heart tube is an endocardial tube, ensheathed by myocardial cells, that develops from bilateral primary heart fields located in the lateral plate mesoderm. Earlier mapping studies of the heart fields performed in whole embryo cultures indicate that all of the myocardium of the developed heart originates from the primary heart fields. In contrast, marking experiments in ovo suggest that the atrioventricular canal, atria and conotruncus are added secondarily to the straight heart tube during looping. The results we present resolve this issue by showing that the heart tube elongates during looping, concomitant with accretion of new myocardium. The atria are added progressively from the caudal primary heart fields bilaterally, while the myocardium of the conotruncus is elongated from a midline secondary heart field of splanchnic mesoderm beneath the floor of the foregut. Cells in the secondary heart field express Nkx2.5 and Gata-4, as do the cells of the primary heart fields. Induction of myocardium appears to be unnecessary at the inflow pole, while it occurs at the outflow pole of the heart. Accretion of myocardium at the junction of the inflow myocardium with dorsal mesocardium is completed at stage 12 and later (stage 18) from the secondary heart field just caudal to the outflow tract. Induction of myocardium appears to move in a caudal direction as the outflow tract translocates caudally relative to the pharyngeal arches. As the cells in the secondary heart field begin to move into the outflow or inflow myocardium, they express HNK-1 initially and then MF-20, a marker for myosin heavy chain. FGF-8 and BMP-2 are present in the ventral pharynx and secondary heart field/outflow myocardium, respectively, and appear to effect induction of the cells in a manner that mimics induction of the primary myocardium from the primary heart fields. Neither FGF-8 nor BMP-2 is present as inflow myocardium is added from the primary heart fields. The addition of a secondary myocardium to the primary heart tube provides a new framework for understanding several null mutations in mice that cause defective heart development.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Waldo
authors.forename: D H
authors.initials: DH
authors.lastname: Kumiski
authors.forename: K T
authors.initials: KT
authors.lastname: Wallis
authors.forename: H A
authors.initials: HA
authors.lastname: Stadt
authors.forename: M R
authors.initials: MR
authors.lastname: Hutson
authors.forename: D H
authors.initials: DH
authors.lastname: Platt
authors.forename: M L
authors.initials: ML
authors.lastname: Kirby
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D018959:CD57 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002642:Chick Embryo; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000096:biosynthesis; D050991:GATA4 Transcription Factor; D006321:Heart / Q000196:embryology*; D006325:Heart Atria / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D011784:Quail; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018959:CD57 Antigens; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D016222:Fibroblast Growth Factor 2; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors