Figure 3. CRX-dependent activated genes affected in opposite directions in developing Crx^E80A and Crx^K88N mutant retinas.

(A) Heatmap showing sample-wise Pearson correlations of the expression of all CRX-dependent activated genes between P10 wild-type (WT) and homeodomain (HD) mutant mouse retinas in this study (rows) with postnatal WT retinas from age P3 to P21 (columns, data from GSE87064). (B) Heatmap showing the expression changes of DEGs in CRX-dependent activated gene set in HD mutant mouse retinas at P10. (C, D) Heatmaps showing expression changes of selected photoreceptor genes from Groups 1 and 2. Color scale identical to (B).

Figure 3—figure supplement 1. Definition of CRX-dependent activated and CRX-independent gene sets.

(A) Schematic representation of CRX-dependent activated genes where CRX binding nearby is required for the expression of these genes in mature wild-type (WT) retinas. (B) Top gene ontology (GO) terms associated with CRX-dependent activated genes. Benjamini–Hochberg adjusted p-values are shown. (C) Line plot showing average expression pattern of CRX-dependent activated genes during normal postnatal retina. (D) Definition of CRX-independent genes where CRX binding nearby is dispensable for the expression of these genes in mature WT retinas. (E) Top GO terms associated with CRX-independent genes. (F) Line plot showing average expression pattern of CRX-independent genes during normal retina development. RNA-seq data in (C) and (F) were retrieved from Aldiri et al., 2017 (GEO accession: GSE87064).

Figure 3—figure supplement 2. E80A and K88N mutation each causes novel gene expression changes in the CRX-independent category.

(A) Strip plots showing normalized CRX ChIP-seq intensity at peaks associated with Group 1 or 2 genes in wild-type (WT) and CRX mutant mouse retinas. p-values for two-sided Mann–Whitney U-test are indicated. (B) Venn diagram showing the overlap of genes differentially expressed (DEGs) in Crx^E80A (pale blue) and Crx^K88N (pale yellow) but not in Crx^R90W/W (gray) mutant retinas. For DEGs in Crx^E80A and Crx^K88N mutants, genes that were differentially expressed in either heterozygotes or homozygotes, or both were counted. (C) Heatmap showing the expression changes of CRX-independent genes that are DEGs in at least one of the Crx^E80A mutants (n = 244, left). Heatmap on the right shows the expression pattern of these genes during normal postnatal development (data from GEO: GSE87064). (D) Table showing selected genes downregulated in Crx^E80A mutants that have been implicated in cell differentiation or photoreceptor development. (E) Heatmap showing the expression changes of CRX-independent genes that are DEGs in at least one of the Crx^K88N mutants (n = 351, left). Heatmap on the right shows the expression pattern of these genes during normal postnatal development (data from GEO: GSE87064). (F) Barchart showing gene ontology (GO) term enrichment of DEGs in Crx^K88N mutants.