Genetic and microstructural differences in the cortical plate of gyri and sulci during gyrification in fetal sheep

Gyrification of the cerebral cortex is a developmentally important process, however the mechanisms that drive cortical folding remain unknown. Theories propose that changes within the cortical plate (CP) cause gyrification, yet differences between the CP below gyri and sulci have not been investigated. Here we report genetic and microstructural differences in the CP below gyri and sulci assessed before (gestational age (GA) 70), during (GA 90) and after (GA 110) gyrification in fetal sheep. The areal density of BDNF-, CDK5-, and NeuroD6-immunopositive cells were increased, and HDAC5 and MeCP2 mRNA levels were decreased, in the CP below gyri compared to sulci during gyrification, but not before. Only the areal density of BDNF-immunopositive cells remained increased after gyrification. MAP2-immunoreactivity was also increased in the CP below gyri compared to sulci at GA 90, and this was associated with microstructural changes assessed via neurite orientation dispersion and density imaging (NODDI) at GA 98. Differential neurite outgrowth may therefore be a strong candidate to explain local changes in CP architecture during gyrification. Overall design: Total RNA of cells coming from gyri or sulci cortical plate from fetal sheep brains at gestational age 90. Four biological replicates, eight samples in total (gyri and sulci per specimen). SPIA sequencing, 7 cycles in Illumina HiSeq3000 sequencer. No technical replicates.