Fibroblast Growth Factor Receptor-1 Is Essential for In Vitro Cardiomyocyte Development

摘要: Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling plays a crucial role in mesoderm formation and patterning. Heartless mutant studies Drosophila suggest that FGFR1, among the different FGFRs, may play cardiogenesis. However, fgfr1 −/− mice die during gastrulation before heart formation. To establish contribution of FGFR1 cardiac development, we investigated capacity murine +/− embryonic stem (ES) cells to differentiate cardiomyocytes vitro. Clusters pulsating were observed >90% 3-dimensional embryoid bodies (EBs) originated from ES at day 9 10 differentiation. In contrast, 10% or less EBs showed beating foci 16. Accordingly, characterized by impaired expression early transcription factors Nkx2.5 d-Hand late structural genes myosin heavy chain ( MHC )-α, -β, ventricular light . Homozygous mutation resulted also alterations mesoderm-related genes, including nodal , BMP2, BMP4 T bra ), sonic hedgehog Nevertheless, similarly express cardiogenic precursor, endothelial, hematopoietic, skeletal muscle markers, indicating -null exerts selective effect on cardiomyocyte development differentiating cells. inhibitors FGFR signaling, tyrosine kinase inhibitor SU 5402, MEK1/2 U0126, protein C GF109 all prevented differentiation without affecting hematopoietic/endothelial marker flk-1 conclusion, data point nonredundant for FGFR1-mediated development.