We also identified two large-scale temporally regulated modules (M20 and M2) with opposite developmental trajectories of genes co-expressed across regions, which either gradually declined (M20) or increased (M2) in expression with age (Supplementary Figs 21 and 22). M20 was enriched for GO categories related to zinc finger proteins (P=7.3×10-48) and transcription factors (P=4.8×10-50), including many ZNF and SOX family members, while M2 was enriched for categories related to membrane proteins (P=1.8×10-21) and genes involved in calcium signaling (P=8.1×10-10), synaptic transmission (P=1.6×10-6), and neuroactive ligand-receptor interaction (P=4.1×10-4), reflecting processes important in postnatal brain maturation. Their hub genes encoded transcriptional factors, modulators of chromatin state, and signal transduction proteins, all of which likely play an important role in driving the networks. Dramatic expression shifts of M20 and M2 in the opposite direction just before birth indicate that this period is associated with transcriptional changes that likely reflect environmental influences on brain development and intrinsic changes in cellular composition and functional processes.
