Differentiation and stemness maintenance of neural stem cells

Neurons of the mammalian central nervous system (CNS) arise from highly polarized, neural stem cells. A defining feature of these cells is their ability to undergo asymmetric divisions, thereby giving rise to one new daughter stem cell and one cell that differentiates into a neuron. This maintenance of self-renewal capacities is of critical importance for brain development. However, so far the mechanisms that balance self-renewal and neuronal differentiation are rather unknown. It has been shown previously that neural stem cells themselves express neuronal differentiation inducing fate determinants like TRIM32. During mitosis, TRIM32 accumulates at the basal pole of the dividing cell and therefore segregates only into one of the daughter cells. After division, TRIM32 induces neuronal differentiation in the inheriting cell. Additionally, neural stem cells also express factors like the PAR3- PAR6-aPKC complex, which are enriched at the apical pole of the dividing cell and are mainly inherited by the new stem cell. The PAR-complex is important for stem cell maintenance, but is also essential for directing cell fate determinants to the opposite pole of the cell. The reason why neural stem cells do not differentiate but maintain their stem cell characteristics, although they express factors that are able to induce neuronal differentiation (such as TRIM32) has not been determined so far. In other words, which molecular mechanisms ensure the maintenance of stemness characteristics in neural stem cells over several rounds of cell divisions?