Interaction of FBXL14 and a Schizophrenia Associated Gene DISC1 in Mouse Embryonic Brain
Date Issued
2014
Date
2014
Author(s)
Huang, Ting-Wei
Abstract
Disrupted in Schizophrenia 1 (DISC1), first identified in human (Homo sapiens), is a disease-related gene that is associated with schizophrenia and other psychiatric disorders including bipolar disorder and autism spectrum disorders (Soares et al, 2011). DISC1 protein is known to be involved in neurodevelopment processes such as neuronal migration (Ishizuka et al, 2011) and neuronal progenitor proliferation (Singh et al, 2010). F-box and leucine-rich repeat protein 14 (FBXL14) is a subunit of E3 ubiquitin ligase complex involved in proteasome-mediated protein degradation (Cardozo et al, 2004). Preliminary data from our lab showed that mouse DISC1 (mDISC1) co-immunoprecipitates (co-IP) with mouse FBXL14 (mFBXL14), suggesting that these two proteins together may play a role in regulating neurodevelopment. To characterize the interaction of mDISC1 and mFBXL14, the deletion constructs of these two genes were prepared to define their respective interaction domains by co-IP assays. GST pull-down assay was also performed to address whether the interactions are via direct binding. Using in utero electroporation (IUEP), we found knock-down of mFbxl14 caused mouse embryonic cortical neurons gathering in the intermediate zone while knock-down of mDisc1 were reported to cause cortical neuron migration defects (Kamiya et al, 2005). How the interaction of mDISC1 and mFBXL14 may affect embryonic cortical neuronal migration and proliferation in vivo was also explored. Through these studies, the molecular basis of the interaction of mDISC1 and mFBXL14 was characterized, which provides insight into the developmental role of mDISC1 and mFBXL14 in the embryonic corticogenesis.
Subjects
schizophrenia
neurodevelopment
neuronal proliferation
neuronal migration
SDGs
Type
thesis
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