FOXP2 regulates differential transcriptional programs in human subplate

Mammalian brains are highly conserved at both the neuroanatomical and gene expression levels. However, the subplate is a neocortical subregion distinguished by a markedly different developmental trajectory among primates compared to other mammals. Moreover, the molecular mechanisms driving these species differences in subplate development remain mostly unknown. Here, we show that human FOXP2, a transcription factor important for speech and language, regulates gene expression programs consistent with subplate neuron expression patterns. These transcriptional profiles have unique overlaps with in vivo data from human fetal brain. We also distinguish DNA-dependent and DNA-independent mechanisms for human FOXP2 to repress patterns of germinal zone expression and promote excitatory neuron gene expression patterns. Overall design: We carried out two RNA-sequencing (RNA-seq) experiments and one ATAC-sequencing (ATAC-seq) experiment in proliferating (hNP) and differentiated (hDN) human neural progenitor cells. For the first RNA-seq, four independent replicates of control and FOXP2-WT over-expressing samples were sequenced in hNPs and hDNs. Three replicates were used in the analysis. For the second RNA-seq three independent replicates of control, FOXP2-WT over-expressing, and FOXP2-KE over-expressing samples were used. The ATAC-seq chromatin was collected in parallel with the second RNA-seq experiment. Four independent replicates of replicates of control, FOXP2-WT overexpressing, and FOXP2-KE overexpressing samples were used. ATAC-seq data and data from the second RNA-seq experiment are published here: DOI:https://doi.org/10.1016/j.celrep.2019.04.044.