Evidence that FGF receptor signaling is necessary for endoderm-regulated development of precardiac mesoderm.
Endoderm cells in the heart forming region (HFR endoderm) of stage 6 chicken embryos are required to support the proliferation and terminal differentiation of precardiac mesoderm cells in vitro. The endoderm's effect can be substituted by growth factors, including members of the fibroblast growth factor (FGF) family. However, direct implication of FGFs in this process requires evidence that inhibition of FGF signaling interferes with proliferation and/or terminal differentiation. This report examines the consequences of treating endoderm/precardiac mesoderm co-explants with agents that inactivate FGF receptors. Using sodium chlorate, which prevents FGF ligand-receptor interaction, it was observed that the percentage of S-phase precardiac mesoderm cells was markedly reduced, suggesting that cell proliferation was inhibited. To more specifically affect FGF signaling, the explants were treated with an antibody that recognizes an extracellular domain of FGF receptor-1 (FGFR-1). This treatment similarly inhibited cell proliferation. Although both agents modestly delayed cardiac myocyte differentiation as indicated by the contractile function, expression of alpha-sarcomeric actin was not affected. These findings provide additional evidence that an intact FGF signaling pathway is required during heart development.
Zhu
X
X
Department of Cell Biology, Neurobiology and Anatomy and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226, USA.
Sasse
J
J
Lough
J
J
D000818:Animals; D002642:Chick Embryo; D004707:Endoderm / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D012965:Sodium Chloride
D017468:Receptors, Fibroblast Growth Factor; D012965:Sodium Chloride; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1