GluD2- and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells

The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, but this hypothesis has not been causally tested in vivo in the mammalian brain. The presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that these dendrite morphogenesis defects result from a deficit in Cbln1/GluD2-dependent competitive interactions. A generative model of dendrite growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis. [Display omitted] •Sparse but not global GluD2 knockout disrupts Purkinje cell dendrite morphogenesis•GluD2 sparse knockout reduces initial but increases subsequent dendritic branching•Competitive dendrite morphogenesis requires GluD2 interactions with ligand Cbln1•A generative model of dendrite growth recapitulates GluD2 manipulation phenotypes Takeo and Shuster et al. find that sparse but not global disruption of GluD2, a synapse organizer, alters cerebellar Purkinje cell dendrite morphology. Genetic experiments and theoretical modeling suggest that a Purkinje cell’s ability to compete for forming synapses with its presynaptic partners in turn regulates its dendrite branching.