We are interested in the molecular mechanisms of neuronal morphogenesis. Cultured hippocampal neurons, in utero electroporation and mouse genetic models are used to explore the mechanisms of neuronal morphogenesis. Neural circuits and behaviors of mutant mice are also investigated to reveal the physiological significance of genes of interest. We have been focusing on the functions of CASK in neurons. CASK, one of causative genes in X-linked mental retardation, is widely distributed in different subcellular compartments of neurons, interacts with various binding partners, and thus performs specific functions. Since CASK acts as a scaffold protein, to investigate the biological significance of CASK, we have been exploring the functions of CASK associated proteins (see figure for the CASK protein network). Interestingly, in addition to CASK, several of these proteins are also relevant to neurological or psychiatric disorders. For instance, Tbr1, NMDAR2b, syndecan-2, Bcl11A, Neurofibromatosis type I (NF1) protein, VCP and CTTNBP2 are associated with autistic spectrum disorder. In addition to NMDAR2b, many target genes of Tbr1 are also the causative genes for either autism or schizophrenia. Our studies investigating the roles of these proteins in neuronal morphogenesis provide the potential explanations how these proteins are relevant to neuropsychiatric disorders. Since VCP is also the causative gene of frontotemporal dementia and amyotrophic lateral sclerosis, our work about the interaction between neurofibromin and VCP provides an example linking neurodegeneration with neurodevelopmental disorder.
There are four major projects in the lab: (1) CASK, mental retardation and autism. (2) Innate immunity and neuronal morphogenesis. (3) The link between neurodevelopment and neurodegeneration- VCP and NF1. (4) CTTNBP2 and neurodevelopment.