Expression of sulfate pathway genes in human neurodevelopment

Sulfate is a vital nutrient for healthy brain development. More than 90 sulfate-related genes are highly conserved across mammalian species, with 16 of these genes being clinically reportable for adverse brain conditions. To determine the potential involvement of additional sulfate-related genes in human neuropathology, this study curated the spatial and temporal expression patterns of all known sulfate biology genes in the human fetal brain from 8 to 37 post conception weeks (pcw) using data from the BrainSpan database and performed network analysis to cluster sulfate-related genes with genes involved in neurodevelopmental processes. A total of 64 sulfate-related genes were abundantly or moderately expressed in 11 brain regions throughout gestation. Steady state expression was observed for some of these genes from 8 to 37 pcw, including genes that encode sulfotransferases (CHST12, CHST7), sulfatases (ARSA, SULF2, TPST1, TPST2), sulfatase modifying enzyme (SUMF2), key enzymes in amino acid metabolism (CDO1, CTH), sulfate transporter (SLC26A11), as well as genes involved in neurodevelopmental processes (ACTG1, TUBA1A, MAPT, UBE3A, DCHS1, WWOX). Between 21-24 weeks, there were numerous clusters of sulfate biology genes with neurodevelopmental genes involved in neuronal migration (FAT4) and synaptogenesis (CBLN2, WNT4, MAPT, FOXP2). At 8-13 and 17-21 pcw, fifteen sulfate genes (ARSF, CHST1, CHST2, CHST13, GAL3ST3, GOT1, IDS, HS3ST2, HS3ST4, HS6ST3, SLC26A8, STS, SULT1A1, SULT4A1, UST) were expressed in the hippocampus and clustered with genes involved in neurogenesis, differentiation and synaptogenesis (MAPT, DNER, NEUROD1). Overall, this study identified 48 sulfate-related genes with moderate/abundant expression in the fetal brain that are coexpressed with genes for neurodevelopmental processes but are not considered in clinical settings. These findings provide information for future studies into the physiological roles of sulfate-related genes that are expressed in the fetal brain.