FGF/MAP kinase signaling is required for <i>nodal</i> expression in the left-right organizer.

<p>A, The early asymmetrical expression of <i>nodal</i> in the endoderm is lost following inhibition of FGFR/MAPK signaling. In embryos treated with the FGF receptor inhibitor SU5402 or the MEK inhibitor U0126 from fertilization onwards, <i>nodal</i> expression is not initiated in the endomesoderm. DAPT treated embryos show bilateral expression of <i>nodal</i> in the endomesoderm but embryos treated with DAPT followed by U0126 treatment at mesenchyme blastula stage do not express <i>nodal</i> in the endomesoderm. B, Inhibition of ERK or FGF signaling randomizes <i>nodal</i> and <i>univin</i> expression in the ectoderm as well as <i>pitx2</i> and <i>sox9</i> expression in the coelomic pouch precursors at pluteus stage. C, Inhibition of MAPK signaling randomizes the positioning of the rudiment. D, Time course of U0126 treatments. Embryos were treated with U0126 starting at the indicated stages and the sidedness of <i>nodal</i> expression was scored at pluteus stage. The efficiency of U0126 treatment on left-right asymmetry drops after 22 hpf, which coincides with the onset of asymmetrical expression of <i>nodal</i> in the endoderm. The percentages and total number of embryos in each experiment are indicated at the bottom of pictures. E, The drop in the ability of U0126 to block <i>nodal</i> expression coincides with the onset of asymmetrical expression of <i>nodal</i> in the endoderm. AV, animal views; DV, dorsal views; L, left; R, right.