The differentiation and integration of the hippocampal dorsoventral axis are controlled by two nuclear receptor genes

The hippocampus executes crucial functions from declarative memory to adaptive behaviors associated with cognition and emotion. However, the mechanisms of how morphogenesis and functions along the hippocampal dorsoventral axis are differentiated and integrated are still largely unclear. Here, we show thatNr2f1andNr2f2genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss ofNr2f2results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency ofNr2f1leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of bothNr2fgenes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover,Nr2f1/2may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating theLhx5-Lhx2axis. Our findings revealed a novel mechanism thatNr2f1andNr2f2converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.