Figure 3.

Hypothetical model showing diversification of neurons as a result of replication stress at CFSs. As neural stem cells (NSCs) proliferate, replication stress (spiked arrow) can result in loss of coordination of the histone deposition and replication process. As a consequence, histones that carry modifications (red circles) are replaced by newly synthesized unmodified histones (green circles). Replication stress at CFSs also causes accumulation of the histone variant macroH2A1.2 (green star). At the genetic level structural variations, like deletions, can arise due to replication stress-induced breaks. The variance at the genetic and the epigenetic level that is caused by replication stress throughout the differentiation of neurons can lead to variance of the expression of the genes located at CFSs. Each individual cell will then have a different expression profile (as indicated by the different colours of cell nuclei), which will eventually lead to a diverse population of neurons that is necessary to perform the complex functions of the brain.