A Role for Atypical Cadherin Celsr3 in Hippocampal Maturation and Connectivity
A Role for Atypical Cadherin Celsr3 in Hippocampal Maturation and Connectivity
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非典型钙粘蛋白 Celsr3 在海马成熟和连接中的作用
DOI：
10.1523/jneurosci.1965-12.2012
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发表时间：
2012-10-03
影响因子：
5.3
通讯作者：
Zhou, Libing
中科院分区：
文献类型：
--
作者：
Feng, Jia;Xu, Ying;Zhou, Libing
非典型钙粘蛋白Celsr3是平面细胞极性的调节因子，对轴突蓝图的发育至关重要。我们以前表明，Celsr3的表达是必要的，以建立前脑连接，如前连合和丘脑皮质和皮质脊髓束。海马布线过程中对Celsr3的需求及其在海马中的作用在很大程度上仍未被探索。在这里，我们比较了Celsr3中海马结构的连接和成熟，|Foxg1和Celsr3| Dlx小鼠。在Celsr3中，Celsr3在整个端脑中失活，包括海马原基，|Foxg1小鼠，Celsr3小鼠端脑基底部早期，包括神经节隆起和腹侧间脑，|Dlx小鼠。行为测试表明，这两个突变体都是过度活跃的，并且有受损的学习和记忆。在Celsr3中发现了CA1、CA3和齿状回的异常细胞构筑|Foxg1突变，其中传入和传出海马通路，以及内在的连接，显着中断。在Celsr3中|在Dlx突变小鼠中，海马细胞结构受到轻度影响，外在和内在连接受到中度干扰。在这两种突变体中，锥体神经元在CA1窝藏萎缩的树突树，突触密度下降，对称与不对称突触的比例增加，和长时程增强被改变。相比之下，突变的海马神经元延长了正常的神经突起，甚至比对照神经元的神经突起更长，这表明体内的异常是继发于有缺陷的连接。出生后的神经发生被保留，突变的中间神经元能够迁移到海马。因此，像在新皮质中一样，Celsr3是海马发育、连接和功能以及锥体细胞成熟所必需的。
Atypical cadherin Celsr3, a regulator of planar cell polarity, is critical for the development of the axonal blueprint. We previously showed that expression of Celsr3 is necessary to establish forebrain connections such as the anterior commissure and thalamocortical and corticospinal tracts. The requirement for Celsr3 during hippocampal wiring and its action in the hippocampus remain largely unexplored. Here, we compared the connectivity and maturation of the hippocampal formation in Celsr3|Foxg1 and Celsr3|Dlx mice. Celsr3 is inactivated in the whole telencephalon, including the hippocampal primordium, in Celsr3|Foxg1 mice, and in the early basal telencephalon, including ganglionic eminences and ventral diencephalon, in Celsr3|Dlx mice. Behavioral tests showed that both mutants were hyperactive and had impaired learning and memory. Abnormal cytoarchitecture of CA1, CA3, and dentate gyrus was found in the Celsr3|Foxg1 mutant, in which afferent and efferent hippocampal pathways, as well as intrinsic connections, were dramatically disrupted. In Celsr3|Dlx mutant mice, hippocampal cytoarchitecture was mildly affected and extrinsic and intrinsic connectivity moderately disturbed. In both mutants, pyramidal neurons in CA1 harbored atrophic dendritic trees, with decreased synapse density and increased proportion of symmetric versus asymmetric synapses, and long-term potentiation was altered. In contrast, mutant hippocampal neurons extended neurites that were normal, even longer than those of control neurons, indicating that anomalies in vivo are secondary to defective connections. Postnatal neurogenesis was preserved and mutant interneurons were able to migrate to the hippocampus. Thus, like in neocortex, Celsr3 is required for hippocampal development, connectivity and function, and for pyramidal cell maturation.