Figure 1.
The expression patterns of Shh, Ptch1, Foxa2 and Gata3 in E11.5 mouse brain from ABA.
Red colors ranging from light to dark indicate the gene expression intensities ranging from low to high. The expression patterns of Shh and Ptch1 defined two adjacent non-overlapping brain domains: Shh+Ptch1− domain and Shh−Ptch1+ domain as shown in supplementary material Figure S1. The anatomical maps were downloaded from ABA and the expression patterns were mapped manually according to the ISH annotation file.
Figure 2.
Genome-wide characterization of Gata3 binding sites in ChIP-seq.
(A) Top binding motif identified by MEME-ChIP. (B) Conservation plot of Gata3 binding sites in vertebrate species. (C) The genome-wide distribution of Gata3-binding sites. (D) The enriched biological processes in Gata3-binding targets revealed by GO analysis.
Figure 3.
The relationship of Gata3 and Foxa2 targets with Shh+Ptch1−-/Shh−Ptch1+-pattern genes.
(A) The overlaps between Foxa2 targets in ChIP-seq with ABA ISH annotations and Shh+Ptch1−-/Shh−Ptch1+-pattern genes. (B) The overlaps between 84 Gata3 targets in ChIP-seq with ABA ISH annotations and Shh+Ptch1−-/Shh−Ptch1+-pattern genes. (C–D) The overlaps between genes with ABA ISH annotations down- or up-regulated by Gata3-knockdown and Shh+Ptch1−-/Shh−Ptch1+-pattern genes. (* indicates the statistical significance of the overlap, P<0.05, in Fisher's exact test).
Figure 4.
Illustration of Gata3 ChIP-seq binding sites on the selected genes.
Red boxes indicate the binding peak locations called by MACS program. (A) Sufu and Gsk3b in the Shh signaling pathway. (B) Slit2/3 involved in axon guidance. (C) Nfasc, Mapt and Limk1 regulating brain development. (D) Qdpr, Th and Slc18a1 involved in neurotransmitter synthesis and release.
Figure 5.
Model of Shh-mediated pattern formation in early mouse brain.
Shh+Ptch1− and Shh−Ptch1+ domains are colored by light red and light blue respectively. Broken line with triangular arrow indicates the diffusion of Shh. Solid line with triangular arrows represent up-regulation while circular arrows represent down-regulation. Two pathways of GLI regulating Gata3 may exist: direct regulation of Gata3 by Gli1/2 (pathway 1)was based on promoter analysis and indirect regulation of Gata3 by GLI through Nkx2.2 as proposed by Craven et al. [56].