BMP signaling regulates Nkx2-5 activity during cardiomyogenesis.
Nkx2-5 regulates the transcription of muscle-specific genes during cardiomyogenesis. Nkx2-5 expression can induce cardiomyogenesis in aggregated P19 cells but not in monolayer cultures. In order to investigate the mechanism by which cellular aggregation regulates Nkx2-5 function, we examined the role of bone morphogenetic protein 4 (BMP4). We showed that the expression of the BMP inhibitor, noggin, was sufficient to inhibit the induction of cardiomyogenesis by Nkx2-5 during cellular aggregation. Furthermore, soluble BMP4 could activate Nkx2-5 function in monolayer cultures, resulting in the formation of cardiomyocytes. Therefore, BMP signaling is necessary and sufficient for the regulation of Nkx2-5 activity during cardiomyogenesis in P19 cells.
Jamali
M
M
Department of Biochemistry, Medical Sciences Building, The University of Western Ontario, London, ON N6A 5C1, Canada.
Karamboulas
C
C
Rogerson
P J
PJ
Skerjanc
I S
IS
D000818:Animals; D015152:Blotting, Northern; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D002352:Carrier Proteins; D002449:Cell Aggregation; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D011506:Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C525812:bmp4 protein, Xenopus