Fig. 8. Mid/hindbrain mutations interfere with cerebellar midline fusion. Whole-mount view (A,C) and midsagittal sections (B, D) through the cerebellum of adult wild-type (A,B) and En1^hd/hd survivor mutants (C,D). Compared to wild type, the velum medullaris is shortened in adult En1^hd/hd mutant survivors (arrowhead in D), and the ependymal surface of the cerebellum is widened (asterisks in B and D) indicating that En1 function is required for the partitioning of the ependymal surface between the velum and the vermis. (E-G) The postnatal cerebellum of Wnt1^sw/sw at P20 (E) and En1^+/Otx2lacZ at P4 (F) has a distinct gap on the midline that is reduced to a fissure in Wnt1^sw/sw adults (G). (H,J) In adult En1^+/Otx2lacZ mutants, the two cerebellar halves are separated by a wide sheet of cells that loops above the surface of the cerebellum (arrowheads). (I) In Wnt1^sw/sw, the anterior cerebellum is fused to the inferior colliculus (arrowhead). (K) Posterior views of E11.5 embryos where the choroid plexus has been labeled by Ttr in situ hybridization. Compared to wild type (wt) and En1^+/Otx2lacZ (En1^Otx2) mutant embryos, the choroid plexus in Wnt1^sw/sw (sw, arrowhead) extends anteriorly separating the cerebellar halves. (L-N) Modification of the cerebellar midline domain in En1^+/Otx2lacZ mutants. (L) Math1 expression is interrupted on the midline in E11.5 embryos. (M,N) Wnt1 expression on the roof plate is prolonged in the hindbrain at E9.5 (compare with wild type; arrowhead, M). This expression becomes wider and fuzzy at later stages (E12.5, N). (O) In Wnt1^sw/sw (sw) mutants at E10.5, Wnt1 expression (purple) is not interrupted in the cerebellar plate as observed in wild type. Axons are labeled in brown by neurofilament immunocytochemistry. (P) Schematic interpretation of the midline phenotypes of Wnt1^sw/sw and En1^+/Otx2lacZ mutants compared to wild type. Same color code as in Fig. 7.

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