In order to better understand the possible connection between PIDD1 and the brain developmental phenotypes observed in individuals with mutations disrupting PIDD1 function, we used publically available transcriptomic datasets (gene expression microarray and RNAseq) for PIDD1, and co-expression with related genes to explore commonalities in temporaspatial expression. Firstly, we used data from the Genotype-Tissue Expression (GTEx) project to explore gross anatomical gene expression for humans through the GTEx Portal (https://www.gtexportal.org/home/ ). Secondly, we used Allen Brain Atlas data (www.brainspan.org ) to look at temporospatial mRNA expression for human brain from 8 weeks post-conception to 40 years of age, using RNAseq and gene expression microarray23 (link), and from RNAseq data from the PsychEncode dataset24 (link). Adult Human transcriptomic comparisons were performed with the Allen Human Brain Atlas data25 (link). Co-expression analysis of BrainSpan datasets was performed as described previously26 (link) (https://hbaset.msl.ubc.ca/ ). Thirdly, we used single-cell RNAseq data from fetal and postnatal mouse brains, for which cell types have been classified according to spatial and taxonomical cluster analysis (www.mousebrain.org )27 (link),28 . Data were analyzed from the single-gene perspective (PIDD1/Pidd1 alone), also with PIDDosome interactors (PIDD1/Pidd1+CRADD/Cradd+CASP2/Casp2), or with a gene set of PIDD1 interactors (P gene set: PIDD1, CRADD, CASP2, MADD, FADD) plus genes relevant to lissencephaly (L gene set: RELN, TUBA1A, NDE1, KATNB1, CDK5, ARX, DCX, LPHN1, LPHN2, LPHN3).
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