Protocadherins Mediate Dendritic Self-Avoidance in the Mammalian Nervous System

DSpace/Manakin Repository

Protocadherins Mediate Dendritic Self-Avoidance in the Mammalian Nervous System

Citable link to this page

 

 
Title: Protocadherins Mediate Dendritic Self-Avoidance in the Mammalian Nervous System
Author: Lefebvre, Julie L.; Kostadinov, Dimitar Vladimirov; Chen, Weisheng V.; Maniatis, Thomas P.; Sanes, Joshua R.

Note: Order does not necessarily reflect citation order of authors.

Citation: Lefebvre, Julie L., Dimitar Kostadinov, Weisheng V. Chen, Tom Maniatis, and Joshua R. Sanes. 2012. Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature 488(7412): 517-521.
Full Text & Related Files:
Abstract: Dendritic arbors of many neurons are patterned by a process called self-avoidance, in which branches arising from a single neuron repel each other. By minimizing gaps and overlaps within the arbor, self-avoidance facilitates complete coverage of a neuron’s territory by its neurites. Remarkably, some neurons that display self-avoidance interact freely with other neurons of the same subtype, implying that they discriminate self from non-self. Here, we demonstrate roles for the clustered protocadherins (Pcdhs) in dendritic self-avoidance and self/non-self discrimination. The Pcdh locus encodes ~60 related cadherin-like transmembrane proteins, at least some of which exhibit isoform-specific homophilic adhesion in heterologous cells and are expressed stochastically and combinatorially in single neurons. Deletion of all 22 Pcdhs in the mouse gamma subcluster (Pcdhgs) disrupts self-avoidance of dendrites in retinal starburst amacrine cells (SACs) and cerebellar Purkinje cells. Further genetic analysis of SACs showed that Pcdhgs act cell-autonomously during development, and that replacement of the 22 Pcdhgs with a single isoform restores self-avoidance. Moreover, expression of the same single isoform in all SACs decreases interactions among dendrites of neighboring SACs (heteroneuronal interactions). These results suggest that homophilic Pcdhg interactions between sibling neurites (isoneuronal interactions) generate a repulsive signal that leads to self-avoidance. In this model, heteroneuronal interactions are normally permitted because dendrites seldom encounter a matched set of Pcdhgs unless they emanate from the same soma. In many respects, our results mirror those reported for Dscam1 in Drosophila: this complex gene encodes thousands of recognition molecules that exhibit stochastic expression and isoform-specific interactions, and mediate both self-avoidance and self/non-self discrimination. Thus, although insect Dscams and vertebrate Pcdhs share no sequence homology, they appear to underlie similar strategies for endowing neurons with distinct molecular identities and patterning their arbors.
Published Version: doi:10.1038/nature11305
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427422/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10636299
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters