Figure 1.

Requirement of free ubiquitin (Ub) above threshold levels for the differentiation of neural stem cells and neuronal development.

If the free Ub amount is above threshold levels, neural stem cell numbers are well maintained, neurogenesis precedes gliogenesis, and mature neurons are generated. However, if the free Ub amount falls below threshold levels, as observed upon Ubb disruption, neural stem cell numbers are reduced due to the impaired self-renewal, gliogenesis occurs prematurely, and defective neurons are generated. Increase in free Ub amount is sufficient to recover neuronal and glial abnormalities to some extent.