Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by non-canonical Wnt signaling,STEM CELLS

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Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by non-canonical Wnt signaling
STEM CELLS ( IF 4.0 ) Pub Date : 2019-11-22 , DOI: 10.1002/stem.3121
Sebastian B Arredondo ₁ , Fernanda G Guerrero ₁ , Andrea Herrera-Soto ₁ , Joaquin Jensen-Flores ₁ , Daniel B Bustamante ₁ , Alejandro Oñate-Ponce ₂ , Pablo Henny ₂ , Manuel Varas-Godoy ₃ , Nibaldo C Inestrosa _{4,

5} , Lorena Varela-Nallar ₁

Affiliation

In the adult hippocampus, new neurons are generated in the dentate gyrus. The Wnt signaling pathway regulates this process, but little is known about the endogenous Wnt ligands involved. We investigated the role of Wnt5a on adult hippocampal neurogenesis. Wnt5a regulates neuronal morphogenesis during embryonic development, and maintains dendritic architecture of pyramidal neurons in the adult hippocampus. Here, we determined that Wnt5a knockdown in the mouse dentate gyrus by lentivirus‐mediated shRNA impaired neuronal differentiation of progenitor cells, and reduced dendritic development of adult‐born neurons. In cultured adult hippocampal progenitors (AHPs), Wnt5a knockdown reduced neuronal differentiation and morphological development of AHP‐derived neurons, whereas treatment with Wnt5a had the opposite effect. Interestingly, no changes in astrocytic differentiation were observed in vivo or in vitro, suggesting that Wnt5a does not affect fate‐commitment. By using specific inhibitors, we determined that Wnt5a signals through CaMKII to induce neurogenesis, and promotes dendritic development of newborn neurons through activating Wnt/JNK and Wnt/CaMKII signaling. Our results indicate Wnt5a as a niche factor in the adult hippocampus that promotes neuronal differentiation and development through activation of noncanonical Wnt signaling pathways.

中文翻译：

Wnt5a 通过非经典 Wnt 信号促进海马中成体神经元的分化和发育

在成年海马体中，新的神经元在齿状回中产生。Wnt 信号通路调节这一过程，但对所涉及的内源性 Wnt 配体知之甚少。我们研究了 Wnt5a 对成年海马神经发生的作用。Wnt5a 在胚胎发育过程中调节神经元形态发生，并维持成年海马锥体神经元的树突结构。在这里，我们确定慢病毒介导的 shRNA 敲低小鼠齿状回中的 Wnt5a 会损害祖细胞的神经元分化，并减少成年出生神经元的树突发育。在培养的成年海马祖细胞 (AHP) 中，Wnt5a 敲低降低了 AHP 衍生神经元的神经元分化和形态发育，而用 Wnt5a 处理具有相反的效果。有趣的是，在体内或体外均未观察到星形胶质细胞分化的变化，表明 Wnt5a 不影响命运承诺。通过使用特定的抑制剂，我们确定 Wnt5a 通过 CaMKII 信号诱导神经发生，并通过激活 Wnt/JNK 和 Wnt/CaMKII 信号促进新生神经元的树突发育。我们的结果表明 Wnt5a 作为成年海马体中的一个利基因子，通过激活非经典 Wnt 信号通路促进神经元分化和发育。

更新日期：2019-11-22

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