The apcCA50a/CA50a is a zygotic-effect mutation resulting in abnormal brain development and aberrant LEF/β-catenin transcription. Lateral view, anterior to the left. (A) Wild-type and apc mutant embryo (B) at 36 hpf. Note the enlarged otic vesicles, smaller irregular eyes, smaller and flattened optic tectum (arrow) and diencephalon (arrowhead) and less discrete MHB. Dashed line indicates the MHB. (C, D) In wild-type embryos at 36 hpf (C), TGFP is restricted to the dorsal midline and posterior boundary of the optic tectum. In apc mutants (D), TGFP is expanded in the tectum, hypothalamus and cerebellum (arrowhead in inset D). Dashed lines indicate MHB and cerebellum. (E, F) Microinjection of a translation-blocking apc1 morpholino (zfapc1 MO) into progeny of apc+/- carriers results in exacerbated phenotypes. (E) The phenotype was categorized according to these categories: wild-type (black), ‘mild’ - reminiscent of apc zygotic phenotype (gray) and ‘severe’ - apc phenotype with additional reduction of eye size, flattening of somites and reduced embryo length (white). In uninjected embryos, only wild-type and ‘mild’ phenotypes were observed. (F) Graph showing the proportion of embryos that show each phenotype. A portion of the embryos in (E, F) was genotyped. Upon injection of 0.1 mM MO, 29% of apc-/- embryos showed a ‘severe’ phenotype (n = 7). Upon injection of 0.25 mM MO, 75% of apc-/- mutants (n = 8) acquired a ‘severe’ phenotype versus only 11% of heterozygous apc+/- embryos (n = 19) and 14% of wild-types (n = 7). Insets - dorsal view. ce, cerebellum; hy, hypothalamus; MHB, mid–hindbrain boundary; re, retina; ot, optic tectum; ov, otic vesicle; tel, telencephalon. Scale bar 250 μm.
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