Nasal shifts in retinal patterning after Fgf-receptor (Fgfr) inhibition. (A-E) epha4b gene expression at the 28 hour stage after Fgfr inhibitor treatment between the 1- and 5-somite stage results in a partial expansion of epha4b from the temporal half into the nasal retina (B). Treatment between the 3- and 8-somite stage (C), and 5- and 10-somite stage (D) induces expansion of epha4b expression throughout the retina. Treatment between the 10- and 15-somite stage has no effect on epha4b expression (E). Mock-treated control in A. Nasal expression of foxg1 (F) and efna5a (G) is absent after treatment between the 5- and 10-somite stage (compare with Fig. 3A,C). (H) Dorsal tbx5 expression is shifted nasally (compare with Fig. 3G), vax2 expression is not altered (I) (compare with Fig. 3I). (K) Gene expression intensity profiling of epha4b in the retina at 28 hours along a clockwise 360° profiling trajectory (J) after Fgfr-inhibitor treatment (mean values, n=3 eyes): comparison of epha4b expression gradients shows the peak in the requirement for Fgfr signaling in retinal NT patterning during the 5- and 10-somite stage (yellow). Treatment periods are color-coded as indicated. Axial positions (in radial degrees of a circle; 0°/360°=ventromedial retina) along the profiling trajectory (x-axis) are plotted against the expression level (mean values of three eyes) in gray values on an 8-bit scale (y-axis). (L) Eye size after Fgfr-inhibitor-treatment along the NT and DV axis compared with wild-type control eyes. Sizes (μm) are mean values (n=9). Images are flat-mounts of dissected eyes, orientation as indicated in A. Dashed outlines indicate the position of the lens. Arrowheads indicate the ventralmost position of the eye marked by the choroid fissure. D, dorsal; V, ventral; N, nasal; T, temporal.
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