Affiliation:
1. Institute for Integrated Cell-Material Sciences (KUIAS-iCeMS), Kyoto University, Kyoto, 606-8501, Japan
2. Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan
Abstract
The mechanism underlying the geometrical patterning of axon and dendrite wiring remains elusive, despite its critical importance in the formation of functional neural circuits. Cerebellar Purkinje cell (PC) arborizes a typical planar dendrite, which forms an orthogonal network with granule cell (GC) axons. By using electrospun nanofiber substrates, we reproduce the perpendicular contacts between PC dendrites and GC axons in culture. In the model system, PC dendrites show a preference to grow perpendicular to aligned GC axons, which presumably contribute to the planar dendrite arborization in vivo. We show that βIII spectrin, a causal gene for spinocerebellar ataxia type 5 (SCA5), is required for the biased growth of dendrites. βIII spectrin deficiency causes actin mislocalization and excessive microtubule invasion in dendritic protrusions, resulting in abnormally oriented branch formation. Furthermore, disease-associated mutations affect the ability of βIII spectrin to control dendrite orientation. These data indicate that βIII spectrin organizes the dendritic cytoskeleton and thereby regulates the oriented growth of dendrites with respect to the afferent axons.
Funder
Japan Society for the Promotion of Science
Takeda Science Foundation
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献