Differential Expression Analysis of the SLIT Family in Different Brain Regions

Here we combine bulk RNA-sequencing of post-mortem tissue (n = 63 across eight regions) with independent validation in the Genotype-Tissue Expression (GTEx) cohort (n = 962) to chart the expression landscape of the 239-member core matrisome. Hippocampus emerged as a major ECM outlier, with 114 matrisome genes—dominated by glycoproteins—up-regulated compared to the other seven regions (Fisher’s combined test, FDR < 0.05).

Genes coding the axon-guidance ligands SLIT1, SLIT2 and SLIT3 ranked among the top hippocampal signatures and displayed strong co-expression with ROBO2 (r > 0.70). Age-stratified analysis in GTEx revealed a concerted decline of the SLIT-ROBO2 axis after 60y, aligning with hallmarks of cognitive ageing. Immunohistochemistry and western blotting (n = 3 per region) supported regional and subcellular patterns of SLITs ROBO2.