ePoster

Schizophrenia risk gene SP4 I: A call for spatio-temporal expression data on fetal radial glial cells and adult nucleus accumbens

Venkiteswaran Muralidhar
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Venkiteswaran Muralidhar

Abstract

SP4 gene is one of the two risk genes implicated in schizophrenia in recent large unpublished case-controlled genomic and exomic sequencing studies. Data on Spatio-temporal SP4 expression in the brain and it's biological functions are sparse in published literature. Bulk RNA sequencing and single-cell high-resolution mid-gestation Spatio-temporal RNA sequencing studies on SP4 from certain brain regions were collated and analysed from published and unpublished databases. The results of bulk RNA sequencing show that SP4 is mainly expressed in the fetal brain. Single-cell RNA sequencing of the mid-trimester fetal brain showed for the first time that SP4 expression in radial glial cells (oRG) is significantly lower than ventricular radial glia (vRG) (P < 0.0001). SP4 increases 1.7 times in oRG from 14-15 weeks to 17-18 weeks, whereas the corresponding temporal increase of SP4 is vRG is 1.4 times, respectively. Furthermore, the results of genomic quantification by eQTL of the principal risk variant in the genomic study, namely rs7811417 (odds ratio (OR) 1.049, P-value is 2.47*10-9), show that it significantly influences the transcription of SP4 in the nucleus acumbens in the post-natal brain (P < 0.00005), with no effect during the developmental stages in the brain. These results suggest that SP4 could be involved in the neurogenesis of layers 2-3 that are putatively known to mediate cognition, a key feature affected in schizophrenia. Moreover, the results also show that the intronic risk variant in the SP4 loci may modulate dopaminergic transmission in the nucleus acumbens that is a site for antipsychotics.

Unique ID: fens-24/schizophrenia-risk-gene-call-spatio-temporal-795fba6e