Another mechanism involved in determining the fate of cells derived from an asymmetrical division of a radial glial stem cell is how the apical protein Par-3 is distributed (Figure 1A). In general, Par-3 maintains the apical-basal polarity of cells. In the developing brain, Par-3 recruits a complex in the apical portion of the cell that can segregate cell-fate-inducing factors, such as Notch signaling proteins. In an asymmetrical division, one daughter cell receives more Par-3 protein than the other (Figure 1B). The daughter cell receiving more Par-3 develops high Notch signaling activity and remains a stem cell. The other daughter cell expresses high amounts of the Delta protein (recall that Delta is the Notch receptor) and becomes primed for neuronal differentiation (Bultje et al. 2009).
It has been shown that the Hes family of Notch-transcriptional effectors exhibit oscillating periods of gene expression in vRG due to a negative feedback mechanism (see Chapters 4 and 17; Shimojo et al. 2008). It is intriguing to speculate about a model in which the number of Notch-Hes oscillations a vRG cell experiences might regulate its developmental fate for renewal, progenitor derivation, or differentiation (Paridaen and Huttner 2014).
Bultje, R. S., D. R. Castaneda-Castellanos, L. Y. Jan, Y. N. Jan, A. R. Kriegstein and S. H. Shi. 2009. Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 63: 189–202.
Paridaen, J. T. and W. B. Huttner. 2014. Neurogenesis during development of the vertebrate central nervous system. EMBO Rep. 15: 351–364.
Shimojo, H., T. Ohtsuka, and R. Kageyama. 2008. Oscillations in notch signaling regulate maintenance of neural progenitors. Neuron 58: 52–64
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