Davis Elizabeth K, Zou Yimin, Ghosh Anirvan
Division of Biological Sciences, Neurobiology Section, UCSD, La Jolla, CA 92093-0366, USA.
Neural Dev. 2008 Nov 5;3:32. doi: 10.1186/1749-8104-3-32.
Wnt proteins comprise a large class of signaling molecules that regulate a variety of developmental processes, including synapse formation. Previous studies have shown Wnts to be involved in both the induction and prevention of synapses in a number of different organisms. However, it is not clear whether the influence of Wnts on synapses is a result of Wnts' behavior in different organisms or differences in the activity of different Wnt ligands.
We used in situ hybridization to show that several Wnt ligands (Wnt3, Wnt5a, Wnt7a, and Wnt7b) and their receptors, Frizzled, are expressed in the developing hippocampus during the period of synapse formation in rodents. We used recombinant Wnt protein or Wnt conditioned media to explore the effects of Wnts on synapses in hippocampal cultures. We found that Wnt7a and Wnt7b activate canonical signaling, whereas Wnt5a activates a noncanonical pathway. The activation of the canonical pathway, either through pathway manipulations or through Wnt stimulation, increases presynaptic inputs. In contrast, exposure to Wnt5a, which activates a noncanonical signaling pathway, decreases the number of presynaptic terminals.
Our observations suggest that the pro- and antisynaptogenic effects of Wnt proteins are associated with the activation of the canonical and noncanonical Wnt signaling pathways.
Wnt蛋白是一大类信号分子，可调节包括突触形成在内的多种发育过程。先前的研究表明，Wnt蛋白在许多不同生物体中参与突触的诱导和抑制。然而，尚不清楚Wnt蛋白对突触的影响是不同生物体中Wnt蛋白行为的结果，还是不同Wnt配体活性差异的结果。
我们使用原位杂交技术表明，在啮齿动物突触形成期间，几种Wnt配体（Wnt3、Wnt5a、Wnt7a和Wnt7b）及其受体卷曲蛋白（Frizzled）在发育中的海马体中表达。我们使用重组Wnt蛋白或Wnt条件培养基来探究Wnt蛋白对海马体培养物中突触的影响。我们发现Wnt7a和Wnt7b激活经典信号通路，而Wnt5a激活非经典信号通路。通过通路操作或Wnt刺激激活经典信号通路会增加突触前输入。相反，暴露于激活非经典信号通路的Wnt5a会减少突触前终末的数量。
我们的观察结果表明，Wnt蛋白的促突触和抗突触生成作用与经典和非经典Wnt信号通路的激活有关。
