5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet 
family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem 
cells (ESCs) and in the brain. However, the role of 5hmC and Tet family in the 
process of ESC differentiation especially neuronal differentiation remains 
elusive. Here, we showed the evidence that Tet3 is critical in neural progenitor 
cell (NPC) maintenance and terminal differentiation of neurons. We found that 
Tet3 expression is basically undetectable in ESCs, but its level increases 
rapidly during neuronal differentiation. Tet3 knockout ESCs appear normal in 
self-renewal and maintenance but impaired in neuronal differentiation. NPCs 
could be induced efficiently from Tet3 knockout ESCs, as the expression of NPC 
marker Pax6 and nestin is comparable with NPCs from wild-type ESCs, but undergo 
apoptosis rapidly, and the terminal differentiation of neurons is greatly 
reduced. Our results indicate that Tet3 is important for NPC maintenance and 
terminal differentiation of neurons.