| Autor: |
Fujishima, Kazuto, Kurisu, Junko, Yamada, Midori, Kengaku, Mineko |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.1101/2020.02.14.945188 |
| Popis: |
The wiring pattern of the neural circuit determines its function and properties. However, the mechanisms underlying the influence of the geometrical patterns of axonal and dendritic arbors on each other remain elusive. The cerebellar circuit displays an orthogonal topology in which Purkinje cell dendrites lie in a single parasagittal plane and form perpendicular contacts with the afferent granule cell axons running along the mediolateral axis. We utilize electrospun nanofibers to align granule cell axons and reproduce perpendicular contacts between Purkinje cell dendrites and granule cell axons in flat culture dishes. We show that the dendritic protein βIII spectrin, a causal gene for spinocerebellar ataxia type 5 (SCA5), is required for the dendritic arborization geometry guided by afferent axonal bundles. βIII spectrin deficiency interferes with the biased growth of dendrites perpendicular to axonal arrays on aligned nanofibers. βIII spectrin deficiency causes the mislocalization of actin and excessive microtubule invasion in dendritic protrusions, resulting in ectopic branch formation in abnormal orientations. We also show that disease-associated mutations affect the ability of βIII spectrin to control dendrite orientation. We provide evidence that βIII spectrin organizes dendritic cytoskeletal structures required to steer the oriented growth of dendrites within neural circuits. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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