Disrupted thyroid hormone function evokes severe physiological consequences in 
the immature brain. In adulthood, although clinical reports document an effect 
of thyroid hormone status on mood and cognition, the molecular and cellular 
changes underlying these behavioural effects are poorly understood. More 
recently, the subtle effects of thyroid hormone on structural plasticity in the 
mature brain, in particular on adult hippocampal neurogenesis, have come to be 
appreciated. However, the specific stages of adult hippocampal progenitor 
development that are sensitive to thyroid hormone are not defined. Using 
nestin-green fluorescent protein reporter mice, we demonstrate that thyroid 
hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b 
and Type 3 progenitors, although it does not alter proliferation of either the 
Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid 
hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, 
and accelerates neuronal differentiation into both DCX-positive immature 
neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we 
show that this increase in neuronal differentiation is accompanied by a 
significant induction of specific transcription factors involved in hippocampal 
progenitor differentiation. In vitro studies using the neurosphere assay support 
a direct effect of thyroid hormone on progenitor development because 
neurospheres treated with thyroid hormone are shifted to a more differentiated 
state. Taken together, our results indicate that thyroid hormone mediates its 
neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and 
suggests a role for proneural transcription factors in contributing to the 
effects of thyroid hormone on neuronal differentiation of adult hippocampal 
progenitors.