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Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity
Journal article   Open access   Peer reviewed

Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

Michael J Molumby, Austin B Keeler and Joshua A Weiner
Cell reports (Cambridge), Vol.15(5), pp.1037-1050
05/03/2016
DOI: 10.1016/j.celrep.2016.03.093
PMCID: PMC4856576
PMID: 27117416
url
https://doi.org/10.1016/j.celrep.2016.03.093View
Published (Version of record) Open Access

Abstract

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. [Display omitted] •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 Molumby et al. manipulate the expression of γ-Protocadherin adhesion molecule isoforms in the mouse cerebral cortex to demonstrate that the complexity of a neuron’s dendritic arbor is promoted by local homophilic interactions with other neurons and with astrocytes.

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