Figure 6. Proposed model of Ub-dependent neural development via regulation of Notch signaling.

Disruption of polyubiquitin gene Ubb reduces levels of cellular Ub pools, resulting in prolonged activation of Notch signaling and impaired neural stem cell (NSC) maintenance or self-renewal. Notch activation during the embryonic stage could lead to dysregulation of NSC differentiation with premature gliogenesis and impaired neurogenesis. Defective neurons may be responsible for activation of astrocytes, which probably cause degeneration (deg.) of defective neurons. Detailed descriptions are provided in the Discussion section.