Fig. 1: Membrane-lipid composition defects precede embryonic lethality in DKO mice.

A Mouse crosses and genotype frequencies at E12.5 (n = 218) and E15.5 (n = 46). See also Supplementary Data 1. B E12.5 embryo showing parts used. C Sections of WT and DKO embryos at E12.5 stained with H&E. (1) surface ectoderm; (2) fourth ventricle; (3) basal plate of metencephalon; (4) trigeminal (V) ganglion; (5) lumen of primitive nasal cavity; (6) olfactory epithelium; (7) third ventricle; (8) optic recess; (9) region of optic chiasma. More sections in Supplementary Fig. 1A–H. D Lipidomics-based PCA of E12.5 heads. Quantities analyzed: mol% of fatty acids species and type (SFA, MUFA, PUFA), and total amount of PE, Cer, DiCer, GlcCer, LacCer, TAG and FC normalized to total PC. Variables used are shown in Supplementary Fig. 1I and Supplementary Data 2. E Volcano plot of lipid species differing between WT and DKO at E12.5, with a p < 0.01 based on t-tests (two sided and assuming normality). Species differing by ≥1% mol are labeled; species measured are in Supplementary Data 2. F Number of proteins identified in WT and DKO embryos at E12.5 and with altered levels (p < 0.01). See Data S3. G GSEA Enrichment plot of the KEGG Fatty Acid Metabolism Pathway. H Gene Set Enrichment Analysis (GSEA) of proteomics data: 16 KEGG pathways are over-represented in DKO embryos at E12.5. See Supplementary Fig. 1K and Supplementary Data 3. I, J Abundance of apolipoproteins in WT and DKO embryos at E12.5. n = 3 biologically independent replicates per condition. K, L PC 32:0 and S1P abundance in brains at E15.5. n = 4, 3, 3 and 1 biologically independent replicate for WT, R1KO, R2KO and DKO, respectively. Lipidomics in Supplementary Fig. 1L and Supplementary Data 2. (n.d. non-detected) I–L shows mean ± SEM and t-tests (two sided and assuming normality) were used to identify significant differences between treatments. **p < 0.01 and *p < 0.05. See Supplementary Fig. 1 and Supplementary Data 1–3. Source data provided as a Source Data file.