Faculty Opinions recommendation of Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly.
Year: 2018
Type: peer-review
Abstract: The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdhα, Pcdhβ, and Pcdhγ).Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb.Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance.By contrast, when endogenous Pcdh diversity is overridden by the expression of a single-tricluster gene repertoire (α and β and γ), OSN axons fail to converge to form glomeruli, likely owing to contact-mediated repulsion between axons expressing identical combinations of Pcdh isoforms.The vertebrate clustered protocadherin Pcdhα, Pcdhβ, and Pcdhγ genes (Fig. 1) generate a high level of cell surface diversity in the nervous system by a mechanism of stochastic promoter choice (1, 2) and assembly of α, β, and γ protein monomers into combinatorial cis homo-or heterodimers that engage in homophilic interactions at the cell surface (3-5).Functional studies in mice revealed that the Pcdhγ gene cluster is required for dendritic selfavoidance in retinal starburst amacrine cells (6).However, it remains unclear why a selfavoidance phenotype was not observed in most other neuronal cell types examined in either Pcdhγ (7-11) or Pcdhα (12) single cluster deletion mutant mice.
Authors: Stephanie Gupton, Shalini Menon
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W4236971849