Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity.
Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity.
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DOI：
10.1016/j.celrep.2016.03.093
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发表时间：
2016-05-03
期刊：
影响因子：
8.8
通讯作者：
Weiner JA
中科院分区：
文献类型：
--
作者：
Molumby MJ;Keeler AB;Weiner JA
适当复杂的树突杆的生长是神经元分化的关键步骤，也是神经回路形成的先决条件。不同的细胞表面分子，如簇状原钙粘附素(Pcdhs)，很早就被提出通过特定的细胞-细胞相互作用来调节电路的形成。在这里，我们使用转基因和条件性基因敲除小鼠来操纵大脑皮层中的γ-Pcdh谱系，我们发现神经元树突状突起的复杂性是由与其他细胞的同嗜性相互作用决定的。仅表达22个γ-Pcdh中的一个的神经元可以表现出旺盛的树突复杂性，也可以表现出最小的树突复杂性，这仅取决于周围细胞是否表达相同的异构体。此外，星形胶质细胞γ-Pcdhs的丢失或星形胶质细胞-神经元亲和性匹配的中断，非自主地降低了树突状细胞的复杂性。我们的数据表明，γ-Pcdhs通过同嗜性匹配在局部促进树突树枝形成，并证实体内的连通性取决于神经元之间以及神经元和星形胶质细胞之间的分子相互作用。
Growth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs), have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron’s dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant, or minimal, dendrite complexity depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching and confirm that connectivity in vivo depends on molecular interactions between neurons, and between neurons and astrocytes.