The Wnt signaling pathway plays key roles in various developmental processes. Wnt5a, which activates the non-canonical pathway, has been shown to be particularly important for axon guidance and outgrowth as well as dendrite morphogenesis. However, the mechanism underlying the regulation of Wnt5a remains unclear. Here, through conditional disruption of Foxg1 in hippocampal progenitors and postmitotic neurons achieved by crossing Foxg1^fl/fl with Emx1-Cre and Nex-Cre, respectively, we found that Wnt5a rather than Wnt3a/Wnt2b was markedly upregulated. Overexpression of Foxg1 had the opposite effects along with decreased dendritic complexity and reduced mossy fibers in the hippocampus. We further demonstrated that FOXG1 directly repressed Wnt5a by binding to its promoter and one enhancer site. These results expand our knowledge of the interaction between Foxg1 and Wnt signaling and help elucidate the mechanisms underlying hippocampal development.

Wnt信号通路在各种发育过程中发挥着关键作用。 Wnt5a 激活非典型途径，已被证明对于轴突引导和生长以及树突形态发生特别重要。然而，Wnt5a 的调控机制仍不清楚。在这里，通过分别将Foxg1 ^fl/fl与Emx1-Cre和Nex-Cre杂交实现海马祖细胞和有丝分裂后神经元中Foxg1的条件性破坏，我们发现 Wnt5a 而不是 Wnt3a/Wnt2b 显着上调。 Foxg1的过度表达会产生相反的效果，即海马中树突复杂性降低和苔藓纤维减少。我们进一步证明 FOXG1 通过结合 Wnt5a 的启动子和一个增强子位点直接抑制 Wnt5a。这些结果扩展了我们对Foxg1和 Wnt 信号传导之间相互作用的了解，并有助于阐明海马发育的机制。