Tbr2 is essential for hippocampal lineage progression from neural stem cells to intermediate progenitors and neurons

Abstract

Neurogenesis in the dentate gyrus has been implicated in cognitive functions, including learning and memory, and may be abnormal in major neuropsychiatric disorders, such as depression. Dentate neurogenesis is regulated by interactions between extrinsic factors and intrinsic transcriptional cascades that are currently not well understood. Here we show that Tbr2 (also known as Eomes), a T-box transcription factor expressedby intermediate neuronal progenitors (INPs),is critically required for neurogenesisin the dentate gyrus of developing and adult mice. In the absence of Tbr2, INPs are depleted despite augmented neural stem cell (NSC) proliferation, and neurogenesis is halted as the result of failed neuronal differentiation. Interestingly, we find that Tbr2 likely promotes lineage progression from NSC to neuronal-specified INP in part by repression of Sox2, a key determinant of NSC identity. These findings suggest that Tbr2 expressionin INPs iscritical for neuronal differentiation in the dentate gyrus and that INPs are anessential stageinthe lineage from NSCs to new granule neurons in the dentate gyrus. © 2012 the authors.