Dendrites from a single neuron manage to avoid crossing, or having contact with, one another. This self-avoidance, which allows dendrites to spread out over the neuron’s territory, is necessary for proper neuronal wiring and postnatal development. Yet dendrites of one neuron may interact with those of another neuron of the same type, indicating that individual neurons are able to distinguish self from non-self. A key question in the mammalian brain is how this is accomplished.
Over a decade ago, the laboratory of Tom Maniatis, PhD, Chairman and Professor of Biochemistry and Molecular Biophysics, discovered a gene cluster that encodes around 60 cell-surface proteins called protocadherins. His laboratory and others discovered that these proteins are expressed in different combinations in individual neurons, thus providing “barcodes” that distinguish one neuron from another. Until now, the function of this barcode remained a mystery. Now Dr. Maniatis and his colleagues at Columbia, along with collaborators in Dr. Josh Sanes’s laboratory at Harvard, report that the protocadherins are required for self-avoidance.
Dendrites are threadlike extensions of neurons that receive impulses and conduct them to the neuron cell body. The researchers used sophisticated genetic methods to remove a subset of protocadherin genes (Pchdg) from specific neurons in mice; they focused on retinal interneurons called starburst amacrine cells (SACs), whose dendrites form a pinwheel-like starburst pattern (left image). In mice lacking the Pcdhg genes in their SACs, the dendrites from a single SAC crossed each other, sometimes forming bundles and clumps (right image). This indicates that Pcdhg genes function in dendritic self-avoidance. The finding is particularly interesting in light of recent reports from whole genome sequencing studies that implicate protocadherins in autism.
“Protocadherins mediate dendritic self-avoidance in the mammalian nervous system” was published online in Nature on July 29, 2012.
The research was supported by NIH grants R01NS029169, R01EY022073, and R01NS043915.