Zic1 LOF up-regulates RA signaling in the forebrain. (A,B) Tailbud stage, rostral view, dorsal to the top. Cyp26a1 expression is strongly reduced in prospective forebrain tissue of Zic1 morphants. (C,D) Lateral view, 18s, anterior to the right. Injection of Z1MO into embryos transgenic for a RA-sensitive gfp reporter leads to a massive up-regulation of reporter activity in anterior neural tissue (arrow) (n = 52, 90%) as compared with control (n = 31). (C′–D′) Anterior view, 18s. Arrow indicates up-regulated reporter expression. Detection of gfp by WMISH due to low signal intensity of the Gfp fluorescence. (E–H) Dorsally expanded pax2 expression in the optic vesicle of Zic1 morphants can be rescued by administration of the RA inhibitor DEAB (brackets indicate dorsal expansion). (G) Pax2 expression in control embryos treated with DEAB is slightly weaker than in controls. (H) Pax2 expression in control embryos. (s) Somite stage.