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Fig. 5 | Molecular Autism

Fig. 5

From: Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development

Fig. 5

Conditional deletion of Chd8 from the embryonic neuroepithelium results in severe hypoplasia of the telencephalon and neocortex. a Schematic representation of the wildtype (wt) mouse Chd8 gene (Chd8wt), targeting construct for homologous recombination in embryonic stem cells, the Chd8 targeted allele (Chd8neo), the Chd8 conditional allele after Flp-mediated excision of the neomycin resistance cassette (Chd8flox) and the Chd8null allele produced by Cre-mediated deletion of exon 3. Boxes represent exons, with exon 1 (Ex1) to 6 and 13 shown and exon 3 filled in black. The blue box represents a neomycin resistance cassette (neo), red triangles represent loxP sites and tan triangles frt sites. The long 9.45 kb (5′) homology arm is indicated in red and the short 4.4 kb (3′) homology arm in green in the targeting construct. b X-gal staining of a Sox1-Cre; R26R embryo at E9.5 (left); and immunostaining for CHD8 protein on Chd8flox/flox (Ctrl) and conditional knockout Sox1-Cre; Chd8flox/flox (cKO) E10.5 neural tube (right). Scale bar = 50 μm. c, d Wholemount images of E18.5 brains of a representative Ctrl and cKO embryo, anterior is to the right. Scale bar = 1 mm. e, f Wholemount images of embryonic day 12.5 heads, anterior to the right. Scale bar = 1 mm. g, h Wholemount images of E10.5 embryos, anterior to the right. c′–h′) Cresyl violet-stained frontal sections through brains as indicated in ch above. Scale bars = 500 μm (c′, d′) and 200 μm (e′–h′). The following subcortical structures are labelled in Ctrl (c′) and cKO (d′) at E18.5: NCtx: Neocortex, mhN: medial habenular nucleus, vmt: ventral medial thalamic nucleus, amN: amygdaloid nucleus. Images are representative of at least 3 independent samples

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