The dominant negative allele <i>Mitf^mi</i> restores retinal development in the <i>Vsx2</i> mutants.

<p>(A–F) Merged images of cryosections showing DAPI staining (blue) and melanogenic pigmentation (white) in P0 <i>orj</i>, <i>R200Q</i>, and <i>R227W</i> mice that were <i>Mitf</i> wild-type (<i>Mitf^+/+</i>; A–C) and <i>mi</i> heterozygous (<i>Mitf^mi/+</i>; D–F). Insets show whole eyes. The retina in C was completely transformed into pigmented tissue (bounded by dashed line) and ectopic POM was partially pigmented (asterisk). Eye size and retinal histology were restored to a comparable degree in all <i>Vsx2</i>, <i>mi</i> compound mutants (D–F). Also notable in the <i>R227W</i>, <i>mi</i> compound mutant was the lack of POM in the vitreal chamber (asterisk in F). (G–L) TUBB3 staining at P0. In all cases, lamination patterns were restored in the compound mutants, indicating robust neurogenesis. Retinal tissue in I is bounded by the dashed lines. (M) The reduced eye size in the <i>R227W</i> mutant was partially rescued in the <i>R227W</i>; <i>Mitf^mi/+</i> mutant at E12.5. (N) The expression of TUBB3 was detected in the <i>R227W</i>; <i>Mitf^mi/+</i> retina at E13.5. (O) <i>Mitf</i> and <i>Otx1</i> transcript levels were much lower in the <i>R227W</i>; <i>Mitf^mi/+</i> retina (black bars) compared to the <i>R227W</i> mutant (white bars). (P) pan-<i>Mitf</i> transcript level in <i>orJ; Mitf^mi/+</i> retina was not lower than that in <i>orJ</i> retina. * P≤0.05; *** P≤0.001 Scale bars: 100 µm (A–F); 1 mm (insets); 50 µm (G–L); 0.5 mm (M); 100 µm (N).