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  • A synaptic molecular dependency network in knockdown of autism- and schizophrenia-associated genes revealed by multiplexed imaging
Title: A synaptic molecular dependency network in knockdown of autism- and schizophrenia-associated genes revealed by multiplexed imaging
The complex functions of neuronal synapses depend on their tightly interconnected protein network, and their dysregulation is implicated in the pathogenesis of autism spectrum disorders and schizophrenia. However, it remains unclear how synaptic molecular networks are altered biochemically in these disorders. Here, we apply multiplexed imaging to probe the effects of RNAi knockdown of 16 autism- and schizophrenia-associated genes on the simultaneous joint distribution of 10 synaptic proteins, observing several protein composition phenotypes associated with these risk genes. We apply Bayesian network analysis to infer hierarchical dependencies among eight excitatory synaptic proteins, yielding predictive relationships that can only be accessed with single-synapse, multiprotein measurements performed simultaneously in situ. Finally, we find that central features of the network are affected similarly across several distinct gene knockdowns. These results offer insight into the convergent molecular etiology of these widespread disorders and provide a general framework to probe subcellular molecular networks.  more » « less
Award ID(s):
1707999
PAR ID:
10561040
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Cell Reports
Date Published:
Journal Name:
Cell Reports
Volume:
42
Issue:
5
ISSN:
2211-1247
Page Range / eLocation ID:
112430
Subject(s) / Keyword(s):
Bayesian network inference CP: Genomics CP: Neuroscience RNAi autism genetic screen molecular network multiplexed imaging schizophrenia siRNA synapse synaptic protein.
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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