
Miley Sinantha-Hu
Bachelor of Science, Honors, Biology with Honors
Masters Student in Biology, admitted Autumn 2019
Minor, Education
Student Employee, Institute for Diversity in the Arts
All Publications
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GluD2- and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells.
Neuron
2020
Abstract
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.
View details for DOI 10.1016/j.neuron.2020.11.028
View details for PubMedID 33352118