Ni Yang, Liu Bin, Wu Xiaojing, Liu Junhua, Ba Ru, Zhao Chunjie
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing, 210009, China.
Neurosci Bull. 2021 Mar;37(3):298-310. doi: 10.1007/s12264-020-00618-z. Epub 2021 Jan 3.
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 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关键作用。激活非经典通路的Wnt5a已被证明对轴突导向、生长以及树突形态发生尤为重要。然而，Wnt5a的调控机制仍不清楚。在这里，通过分别将Foxg1与Emx1-Cre和Nex-Cre杂交，有条件地破坏海马祖细胞和有丝分裂后神经元中的Foxg1，我们发现Wnt5a而非Wnt3a/Wnt2b显著上调。Foxg1的过表达具有相反的效果，同时海马体中的树突复杂性降低，苔藓纤维减少。我们进一步证明，FOXG1通过结合其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与Wnt信号之间相互作用的认识，并有助于阐明海马体发育的潜在机制。
