Theses and Dissertations Collection

The intricate organization of the neurons and synapses that make up the human nervoussystem is fundamental to our ability to interact with the world around us. The proper function of these networks relies heavily on the proper organization of neurons and their processes during development. Disruptions to this process can result in developmental and degenerative pathologies, including autism spectrum disorders, Down Syndrome, and blindness. Successful neural organization relies on interactions between molecules that couple neurons to their appropriate partners, followed by synaptic activity to solidify the neural connections between those partners. Here, we focus on a cell adhesion molecule family, the Down Syndrome Cell Adhesion Molecules (Dscams), and their roles in signaling and how these processes contribute to neural development, and their loss to degeneration through several studies. In the first study, we demonstrate that retinal neurons maintain a level of plasticity after maturity that allows modification of their receptive fields and synapses based on cellular density. In the second study, we test the requirement of Dscaml1 in the formation and maintenance of the rod-to- rod bipolar cell synapses during aging. We show that the rod-to-rod bipolar cell synapse is properly formed and maintained through aging even in the absence of Dscaml1. However, the number of neurite invaginations in rod spherules increases even though the number of dendritic tips on rod bipolar cells is reduced. We also demonstrate that loss of Dscaml1 results in smaller, and less complex, mitochondria that may provide insight into the possibility that intracellular changes may contribute to diseases linked to mutations in Dscaml1, including congenital stationary night blindness. In the third study, we use a unique Dscaml1 loss of function model to map the expression of Dscaml1 in the mouse brain that adds versatility when compared to antibody and in situ labeling which are limited by availability and nuclear labeling. While incorporating undergraduate education, we generated a reference tool that shows Dscaml1 expression in both cell bodies and axon tracts. Finally, we tested possible downstream interactions of DSCAM by utilizing loss and gain of function mouse models to measure genetic interactions between Dscam and Dyrk1a. We provide evidence that Dyrk1a acts downstream of Dscam in several aspects of neural development including developmental cell death and neurite lamination, and that DSCAM regulates DYRK1A location and concentration within the mouse brain. These works contribute to understanding how Dscams regulate and contribute to neural development and degeneration, provide insight into the underlying mechanisms of how a single cell adhesion molecule can regulate multiple processes throughout development, and set the groundwork in targeting cell adhesions molecules as novel therapeutic targets in many neural pathologies.