Fig. 4

Zmynd11 deficiency alters the transcriptome and disrupts PI3K signaling pathway. A Heatmap shows differentially expressed genes (DEGs) between scramble and Zmynd11 KD eNPCs. B Gene ontology (GO) analysis showed that upregulated genes were highly enriched for the terms related with T cell activation and proliferation in Zmynd11 KD eNPCs. C GO analysis showed that downregulated genes were highly enriched for the terms related with neuronal development in Zmynd11 KD eNPCs. D KEGG analysis showed the upregulated pathways in Zmynd11 KD eNPCs. E KEGG analysis showed the downregulated pathways including PI3K signaling pathway in Zmynd11 KD eNPCs. F Gene Set Enrichment Analysis (GSEA) map of influenced genes in PI3K signaling pathway. G–L qRT-PCR assay results showed that Zmynd11 KD significantly reduced the mRNA level of Epha2 (G), Osmr (H), Ngf (I), Lama3 (J), Col6a1 (K), Ccnd2 (L), key components of PI3K signaling pathway. n = 3 biologically independent experiments. Data are presented as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001, unpaired Student’s t-test. M Representative WB images of Zmynd11, Epha2, IRS1, p-IRS1, PI3K, p-PI3K, PDPK1, p-PDPK1, SGK1, p-SGK1 in the cortical tissues of Ctrl and cKO mice. Tubulin and GAPDH were used as internal controls. N–V Quantification results showed that level of Epha2 was significantly decreased in the brain of cKO mice compared to Ctrl (N). The levels of total IRS1 (O), PI3K (P), PDPK1 (Q), and SGK1 (R) showed no difference between Ctrl and cKO mice, but the levels of p-IRS1 (S), p-PI3K (T), p-PDPK1 (U), and p-SGK1 (V) were remarkably decreased in cKO mice compared to Ctrl. n = 4 biologically independent experiments. Data are presented as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, unpaired Student’s t test