Finding Down Syndrome Cell Adhesion Molecule (DSCAM) Protein Interactions in Pathways of Neuronal Development

Down Syndrome cell adhesion molecule (DSCAM) is a transmembrane protein that has a significant role in proper neurodevelopment by promoting self-avoidance in neurons. This project aims to identify proteins that interact with DSCAM in the mouse brain by using a library of plasmids. The plasmid library was tested for proteins that interact with the C-terminus end of DSCAM in Brewer’s yeast (S. cerevisiae). By using the bait and prey method from a yeast two-hybrid system, mouse brain proteins were tested for true interaction with DSCAM. Proteins that interact with DSCAM allow the yeast to produce their own leucine, which aids in the growth of the yeast on selective media. Proteins that have been identified as possible protein interactors include COX5B, NEFL, ELAV1, and SOD1, among others. By identifying interactions between unknown proteins and DSCAM, we will be better able to map out the protein interactions that lead to the proper development of the brain

Gene Mutations Involved in Brain Development and Autism Spectrum Disorders

Genetic factors have been found to contribute to Autism Spectrum Disorder (ASD), a developmental disability characterized by sensory and communication deficits, but current treatment only involves therapy and antipsychotic medications. Finding a model of gene mutations associated with ASD can assist in the development of novel forms of treatment for patients diagnosed with these genetic mutations. Down Syndrome Cell Adhesion Molecule Like-1 (DSCAML1) has been previously studied in mice to have significant effects on developing mouse retinas, but these studies have not extended into other regions of the brain where Dscaml1 is expressed. Initial analyses using expression staining on loss of function Dscaml1 mice has suggested that the superior colliculus and the hippocampus show variation in expression compared to wild type mice. The superior colliculus is involved with sensory processing of visual information, and the hippocampus functions in learning and memory. Comparison of the superior colliculus, the hippocampus, and more regions of the brain that are affected between these mutant mice and people with Dscaml1 mutations may allow for better understanding of DSCAML1’s impact on brain function and development to determine if mice will make a good model to test clinical interventions for ASD treatment