DEV01946 Supplementary Material

Files in this Data Supplement:

• Supplemental Figure 1 - Fig. S1. Expression pattern of a nestin-Psen1 transgene. (A,B) Horizontal sections through the telencephalon of an E13.5 nestin-Psen1 transgenic (A) or non-transgenic littermate control (B) embryo hybridized with a human-specific PSEN1 probe. There is prominent hybridization in the ventricular zone (indicated by the arrow) surrounding the lateral ventricles (V) and an absence of signal in the non-transgenic specimen. Scale bar: 200 mm.

• Supplemental Figure 2 - Fig. S2. Rescue of leptomeningeal abnormalities in Psen11^–/– embryos with a nestin-Psen1 transgene. Cresyl Violet-stained horizontal sections from the lateral telencephalon of E18.5 embryos that are wild type (A), Psen1^–/– (B) or have the nestin-Psen1 transgene on the Psen1^–/– background (C). The leptomeninges are marked with asterisks. The Psen1^–/–embryo displays the leptomeningeal thickening (B), which is normalized in the embryo with the nestin-Psen1^–/– transgene on the Psen1^–/– background (C). Scale bar: 50 mm.

• Supplemental Figure 3 - Fig. S3. Restoration of chondroitin sulfate proteoglycan expression in the marginal zone of Psen1^–/– embryos by a nestin-Psen1 transgene. Immunohistochemical staining for CSPG (red) combined with a DAPI nuclear stain (blue) through the lateral cerebral wall of E18.5 embryos that are wild type (A) or Psen1^–/– (B), or express the nestin-Psen1 transgene on the Psen1^–/– background (C). The marginal zone (MZ) and cortical plate (CP) are indicated. CSPG immunoreactivity is lost in the Psen1^–/– marginal zone (B) and restored when the nestin-Psen1 transgene was bred onto the Psen1^–/– background. An ectopia in the marginal zone of the Psen1^–/– brain is indicated by an arrow (B). Scale bar: 50 mm.

• Supplemental Figure 4 - Fig. S4. Normal appearance of Cajal-Retzius cells in Psen1^–/– embryos expressing a nestin-Psen1 transgene. Reelin immunostained sections through the lateral cerebral wall of E18.5 embryos that are wild type (A,D) or Psen1^–/– (B,E), or have the nestin-Psen1 transgene on the Psen1^–/– background (C,F). Cajal-Retzius cells (indicated by arrows) are stained in the marginal zone of all three embryos. (D-F) Higher power views of reelin-stained cells. Cajal-Retzius cells appeared modestly depleted in the Psen1^–/– embryos but normal in number when the nestin-Psen1 transgene was bred onto the Psen1^–/– background. Scale bars: 50 mm in A-C; 10 mm in D-F.

• Supplemental Figure 5 - Fig. S5. Normal patterns of BrdU labeling in E12.5 embryos with or without Psen1. Pregnant females mice received one injection of BrdU 2 hours prior to sacrifice. BrdU immunostaining of horizontal sections from wild type (A,B), Psen1^+/– (C,D), Psen1^–/– (E,F), nestin-Psen1 transgene on Psen1^–/– background (G,H) and nestin-Psen1 transgene on Psen1^+/+ background (I,J) are shown. (B,D,F,H,J) Higher power images of labeling through the lateral cerebral wall. The preplate (PP) and ventricular zone (VZ) are indicated in B. No differences were apparent between any of the genotypes. Scale bar: 80 mm for A,C,E,G,I; 10 mm for B,D,F,H,J.