To understand the biological roles of splicing regulators and their impact on neuronal development and function, we have developed conditional knockout mice for multiple proteins. Collaborating with a variety of UCLA neuroscience groups, these mice are examined for defects in development, mature physiological function, and behavior. We use viral transduction and genome editing methods in primary neuronal culture and stem cell differentiation models to assess the effect of individual proteins on particular splicing targets. Through these studies, we have shown that the PTBP2 protein controls a program of gene expression required for neuronal maturation. And we have found that the Rbfox proteins play important roles both in cerebellar development and in controlling neuronal excitation in the mature hippocampus. In additional projects, we have examined how the PTB and Rbfox proteins affect other cellular processes such as miRNA biogenesis and translation.
