Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

•Increasing γ-Pcdh homophilic matching promotes dendrite complexity in the cortex•Inducing γ-Pcdh homophilic mismatching reduces dendrite complexity in the cortex•Astrocytes regulate dendrite complexity cell non-autonomously via γ-Pcdh interactions•γ-Pcdhs promote dendrite complexity through local interactions

SummaryGrowth 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 they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes.

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