Investigating the neuronal function of ZNF185

Project Summary Intellectual disability (ID) and autism spectrum disorder (ASD) are caused by a wide variety of environmental and genetic factors. Zinc-finger proteins (ZNF) are among the most abundant proteins expressed in eukaryotes, are involved in a wide variety of cellular processes. Numerous studies have shown that many ZNF family members are linked to neurologic disorders, including ID and ASD. ZNF185 is a member of this family, comprised of an actin filament-binding domain and a single zinc-finger containing LIM domain. ZNF185 has been suggested to act as a tumor suppressor gene, but it is otherwise an understudied protein with no known function in the nervous system. Our preliminary data indicate that ZNF185 is highly expressed in the adult hippocampus, and it is enriched in the presynaptic compartment of excitatory synapses. We hypothesize that ZNF185 regulates synaptic function, and that its disruption could lead to impaired cognition and autistic behaviors. To test this hypothesis, we will use a recently developed ZNF185 knockout mouse model. In the first aim, we will use super- resolution imaging and acute slice electrophysiology to examine the role of ZNF185 in synaptic development and function. In the second aim, we will examine the effects of ZNF185 knockout on brain development and behavior. The successful completion of this proposal will determine how ZNF185 regulates neural development, synaptic function, and behavior, with important implications for our understanding of neurologic disorders such as ID and ASD.