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Fig. 6. Midbrain development. (A-D) Whole-mount in situ hybridization on E11.5 embryos. Expression of molecular markers in the ventral midbrain in wild type (A,C) and Psen1 mutant (B,D) embryos. (A,B) F-spondin expression is specifically downregulated in the ventral midbrain (and diencephalon), but unaffected in the hindbrain of the mutant. (C,D) By contrast, no differences are detected in the expression pattern of Lmx1a between wild type (C) and mutant (D). (E-H) Anlagen of midbrain nuclei are formed abnormally in the Psen1 mutants. (E,F) Flat-mount preparations of E11.5 embryos, ventricular view; anterior towards the top. The oculomotor complex, which is detected by Gata3 expression, is smaller in the mutant (F) in comparison with wild type (E). (G-J) Midbrain dopaminergic neurons (DA), detected by Th expression at E11.5, develop close to the ventral midline in the wild-type (G) but are continuous across the midline in the mutant (H). (I,J) At late embryonic stages (E17.5), DA neurons remain clustered at the midline of the mutant (J). Notice ectopic cluster of Th-positive neurons (arrow in J). Coronal sections through E11.5 (G,H) and E17.5 (I,J) embryos. aq, aqueduct; red arrowheads in H,J indicate the midline.





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