UCSF

Understanding the molecular agents that direct and maintain synaptic connectivity and structure in the central nervous system (CNS) is critical in addressing many neurocognitive disorders. Mutations in cell adhesion proteins (cadherins) that direct cell-type specific connectivity have been associated with autism, bipolar disorder and schizophrenia. The retinal-tectal projection, with its mutual laminar organization, provides a unique model system to identify cell type-specific cadherin expression and interrogate its mechanism. The central goal of this thesis is to identify candidate cadherins associated with restricted populations in the superior colliculus (SC) and to determine their role in directing circuit formation with retinal ganglion cell projections. In this study, Cadherin 13 is identified as a candidate cell adhesion protein in SC wide field cells. Cdh13 is a homophilic type 2 cadherin whose mutation is associated with ADHD, bipolar disorder, depression, autism and schizophrenia in human GWAS studies . In the CNS, Cdh13 has been shown to be involved in axon targeting and synapse regulation. This thesis explores the role of Cdh13 in cell type-specific pathway maintenance between the retina and wide field cells. Chapter 1 describes new and necessary methods for consistent laminar and transsynaptic analysis that were developed during this research and can be expanded to further experiments and regions. Chapter 2 explores Cdh13’s expression patterns in conjunction with its temporal and spatial necessity in connectivity structures between the retina and SC. Chapter 3 presents preliminary results further interrogating Cdh13’s mechanisms in retinal-tectal connectivity. The culmination of these chapters not only detail Cadherin 13’s role in cell-type specific interactions between the retina and the SC, but also build upon established institutions to provide improved methods and updated information for future studies.