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Fig. 7. Gata4 regulates an Erbb3-Erk pathway required for EMT. (A)
E9.5 control or Gata4T2del embryos were cultured in M199
containing 100 ng/ml heregulin. A phosphospecific Erk antibody (pErk; green
staining) showed defective Erk ativation in the endocardium of mutant embryos
(arrowheads, bottom panel) compared with control embryos (arrowheads, middle
panel). Myocardial pErk levels were unchanged between genotypes. To
demonstrate antibody specificity, a control embryo was incubated with U0126, a
selective inhibitor of Erk activation (top panel). (B) U0126 (10 µM)
blocked the formation of mesenchymal cells in wild-type AV explants.
(C) Synthetic phenotype resulting from the combination of reduced Gata4
expression and partial Erk inhibition. Explants from embryos homozygous for a
hypomorphic Gata4 allele (H/H) underwent EMT at the same rate as controls in
the presence of vehicle (NS, no significant difference). However, in the
presence of U0126 at a 50% inhibitory dose, EMT was strongly inhibited in
hypomorphic explants (*P<0.05 compared with
control-treated H/H or U0126-treated wt/wt; n=4). The extent of EMT
was measured by the number of cells with mesenchymal morphology that invaded
the collagen gel.
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