Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity.
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.
Department of Biology, The University of Iowa, Iowa City, IA 52242, USA; Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA.
Michael J
MJ
Molumby
Department of Biology, The University of Iowa, Iowa City, IA 52242, USA; Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA.
Austin B
AB
Keeler
Department of Biology, The University of Iowa, Iowa City, IA 52242, USA; Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA; Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA; Department of Psychiatry, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: joshua-weiner@uiowa.edu.
Joshua A
JA
Weiner
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication; D002540:Cerebral Cortex / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D008822:Mice, Transgenic; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism
D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D020033:Protein Isoforms