Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in the endocardial cushion and adjacent tissues of the developing mouse heart.
The bone morphogenetic proteins BMP-2 and BMP-4 and the homeobox gene MSX-2 are required for normal development of many embryonic tissues. To elucidate their possible roles during the remodeling of the tubular heart into a fully septated four-chambered heart, we have localized the mRNA of Bmp-2, Bmp-4, Msx-2 and apoptotic cells in the developing mouse heart from embryonic day (E)11 to E17. mRNA was localized by in situ hybridization, and apoptotic cells by TUNEL (TDT-mediated dUTP-biotin nick end-labeling) as well as by transmission electron microscopy. By analyzing adjacent serial sections, we demonstrated that the expression of Msx-2 and Bmp-2 strikingly overlapped in the atrioventricular canal myocardium, in the atrioventricular junctional myocardium, and in the maturing myocardium of the atrioventricular valves. Bmp-4 was expressed in the outflow tract myocardium and in the endocardial cushion of the outflow tract ridges from E12 to E14. Msx-2 appeared in the mesenchyme of the atrioventricular endocardial cushion from E11 to E14, while Bmp-2 and Bmp-4 were detected between E11 and E14. Apoptotic cells were also detected in the mesenchyme of the endocardial cushion between E12 and E14. Our results suggest that BMP-2 and MSX-2 are tightly linked to the formation of the atrioventricular junction and valves and that BMP-4 is involved in the development of the outflow tract myocardium and of the endocardial cushion. In addition, BMP-2, BMP-4 and MSX-2 and apoptosis seem to be associated with differentiation of the endocardial cushion.
Abdelwahid
E
E
Department of Pediatrics and MediCity Research Laboratory, University of Turku, Finland. eltyeb.abdelwahid@utu.fi
Rice
D
D
Pelliniemi
L J
LJ
Jokinen
E
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001283:Atrioventricular Node / Q000196:embryology / Q000502:physiology; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004699:Endocardium / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006351:Heart Valves / Q000196:embryology / Q000502:physiology; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta