[PDF][PDF] Homophilic protocadherin cell-cell interactions promote dendrite complexity

MJ Molumby, AB Keeler, JA Weiner - Cell reports, 2016 - cell.com
MJ Molumby, AB Keeler, JA Weiner
Cell reports, 2016cell.com
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 …
Summary
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 they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes.
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