H3 Acetylation-Induced Basal Progenitor Generation and Neocortex Expansion Depends on the Transcription Factor Pax6

<p>The mammalian cerebral cortex is believed to have gained complexity partly because of the abundance of specific cell types, collectively called basal progenitors. If these cells are deficient in the developing brain, it can lead to cortical structure anomalies, which have implications for defective brain function. Certain regulatory molecules have been found to control the production of basal progenitors during brain development. Key amongst them is the Paired Box 6 (Pax6) transcription factor and a chromatin modification mark called histone 3 lysine 9 acetylation (H3K9ac). However, our knowledge of how these regulatory factors interact to drive the generation of basal progenitors is insufficient. In this current work, we found that the enzyme involved in the acetylation of histone 3 at the 9th lysine interacts with Pax6 at the loci of genes critical for the production and amplification of the basal progenitor cell pool. As such, when both factors are decoupled or downregulated, it leads to depletion of the basal progenitor cells, resulting in a reduction in cortical development. The new mechanism identified deepens our understanding of cerebral cortex development and provides potential therapeutic cues for remedying brain abnormalities stemming from basal progenitor cell deficiency. </p>