Cux2 regulates neurogenesis in the postnatal mouse hippocampus

Abstract

Although once thought to be incapable of regeneration, the adult mammalian brain generates new neurons in two regions: the SVZ of the lateral ventricle and the DG of the hippocampus. While the cell types involved in adult neurogenesis have been broadly characterized, the transcriptional regulation of this process remains poorly understood. Here, we demonstrate that transcription factor Cux2 is important for normal postnatal hippocampal neurogenesis. Cux2neo/neo mutant mice generated fewer Dcx-positive neuroblasts, Tbr2-positive transit amplifers, and Calretinin-positive immature neurons, without affecting gliogenesis. Moreover, we show that Cux2 is principally expressed in Type1/Type2a cells. Using cultured embryonic NPCs we show that Cux2 mutants generate fewer neurons. Indeed, Cux2 plays a pro-neuronal role in both the postnatal hippocampus and in cultured embryonic NPCs. Cux2 may thus serve as an important regulator of the neuronal fate and may be a novel marker for neuronally committed Type 1/2a NPCs in the postnatal DG.