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Fig. 7. Development of the cerebellum and precerebellar nuclei. (A-D) Development of the external granular layer and the Purkinje cells, detected respectively by Math1 and Rora expression in wild type (A,C) and Psen1 mutant (B,D) embryos. (A,B) GCP generation and spreading are compromised in the mutant. A,C and B,D are adjacent, mid-sagittal sections through E17.5 cerebellum. (C,D) Purkinje cells form clusters in the mutant beneath the EGL (D). In the mutant (B,D), there is overgrowth of caudal midbrain (asterisks) and presence of medial tissue (indicated by two white lines and black arrow) devoid of GCPs and PCs. (E-J) Coronal sections through E17.5 cerebellum at the levels (e and g, i) indicated by white lines in A. Midline fusion of posterior cerebellum is incomplete in the mutant. (E-H) In situ hybridization with Pax6 identifies GCPs. Cerebellar morphology is affected medially (F) and posterior cerebellum remains unfused in mutant (asterisk in H) when compared with wild type (E,G). This morphogenetic defect causes GCPs to cluster (H). (I,J) PCs, which are identified by Rora expression, assume positions beneath the normally developing EGL in wild type (I) and the displaced EGL in the mutant (J). (K,L) Pontine migratory stream and pontine nucleus proper detected by Pax6 expression at E16.5. The migratory stream is underpopulated, Pax6-expressing cells accumulate ectopically (arrow in L) and the pontine nucleus (pn) is severely underdeveloped in the mutant (L). In situ hybridization on sagittal (A-D and K,L) and coronal (E-J) sections through caudal midbrain and cerebellum at E17.5 (A-J) or E16.5 (K,L).

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