Significance of bone morphogenetic protein-4 function in the initial myofibrillogenesis of chick cardiogenesis.
The heart is the first organ to form and function during vertebrate embryogenesis. Using a secreted protein, noggin, which specifically antagonizes bone morphogenetic protein (BMP)-2 and -4, we examined the role played by BMP during the initial myofibrillogenesis in chick cultured precardiac mesoendoderm (mesoderm + endoderm; ME). Conditioned medium from COS7 cells transfected with Xenopus noggin cDNA inhibited the expression of sarcomeric proteins (such as sarcomeric alpha-actinin, Z-line titin, and sarcomeric myosin), and so myofibrillogenesis was perturbed in cultured stage 4 precardiac ME; however, it did not inhibit the expression of smooth muscle alpha-actin (the first isoform of alpha-actin expressed during cardiogenesis). In cultured stage 5 precardiac ME, noggin did not inhibit either the formation of I-Z-I components or the expression of sarcomeric myosin, but it did inhibit the formation of A-bands. Although BMP4 was required to induce expressions of sarcomeric alpha-actinin, titin, and sarcomeric myosin in cultured stage 6 posterolateral mesoderm (noncardiogenic mesoderm), smooth muscle alpha-actin was expressed without the addition of BMP4. Interestingly, in cultured stage 6 posterolateral mesoderm, BMP2 induced the expressions of sarcomeric alpha-actinin and titin, but not of sarcomeric myosin. These results suggest that (1) BMP4 function lies upstream of the initial formation of I-Z-I components and A-bands separately in a stage-dependent manner, and (2) at least two signaling pathways are involved in the initial cardiac myofibrillogenesis: one is an unknown pathway responsible for the expression of smooth muscle alpha-actin; the other is BMP signaling, which is involved in the expression of sarcomeric alpha-actinin, titin, and sarcomeric myosin.
Nakajima
Yuji
Y
Department of Anatomy, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. yuji@med.osaka-cu.ac.jp
Yamagishi
Toshiyuki
T
Ando
Katsumi
K
Nakamura
Hiroaki
H
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014981:Xenopus; D029867:Xenopus Proteins; D000099176:Noggin Protein
D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D011506:Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D000099176:Noggin Protein; C525812:bmp4 protein, Xenopus