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

Abstract

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 that <i>Nr2f1</i> and <i>Nr2f2</i> genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss of <i>Nr2f2</i> results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency of <i>Nr2f1</i> leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of both <i>Nr2f</i> genes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover, <i>Nr2f1/2</i> may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating the <i>Lhx5-Lhx2</i> axis. Our findings revealed a novel mechanism that <i>Nr2f1</i> and <i>Nr2f2</i> converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.