In the vertebrate cerebellum, Purkinje cells (PCs) make highly branched dendrites that are remarkable for their restriction to a single, parasagittal plane. The dendrites connect to perpendicular parallel fibres of cerebellar granule cell (GC) axons, which form before them in development and are thought to be required for dendrite planarity. However, the molecular control of dendritic branching remains incompletely understood. Now Kazuto Fujishima and colleagues reveal a crucial role for the βIII spectrin subunit in PC dendrite development (spectrins are cytoskeletal scaffolds that line the inside of the cell membrane and bind actin). Cell-autonomous βIII spectrin knockdown leads to PC dendrites extending away from the main plane. When plated on electrospun nanofibres, GC axons run parallel to aligned fibres, whereas PC dendrites grow in a perpendicular direction. This perpendicular bias is lost following βIII spectrin knockdown; αII spectrin knockdown had similar effects. Time-lapse imaging reveals that biased dendritic growth leads to PC perpendicular orientation, and lateral branching increases following βIII spectrin knockdown. As seen in vivo, plated PCs show dense protrusions covering the lateral surface of the dendritic shaft; these protrusions are misshapen in βIII spectrin knockdown cells, and both actin localisation and microtubule polymerisation are aberrantly enriched in them. Finally, spinocerebellar ataxia type 5-associated βIII spectrin mutations disrupt dendritic orientation, both in vivo and in vitro. Thus, βIII spectrin crucially controls the planar branching of PC dendrites.
