Karla Bernardo


δ-catenin Expression in Neural Development

δ-catenin is a protein encoded by the gene CTNND2 on chromosome 5 and has been shown to affect cognitive function when mutated or insufficiently expressed. Mutations of a portion of the gene has been linked to Cri-du-Chat syndrome and specific forms of autism, and δ-catenin has been shown to interact with Presenilin 1, a protein affiliated with familial Alzheimer's disease. Given the evidence for a correlation between levels of δ-catenin and efficacy of the central nervous system, our research focuses on the role of δ-catenin in neural development and neural networks to more accurately define how knocked down expression of the protein alters cellular function as cells mature and differentiate. Using lentiviruses that express human-specific and mouse-specific short-hairpin RNA to knockdown gene expression in stem cells, we are able to screen the human MCF7 cells to determine the shRNA that best knocks down δ-catenin expression. We extracted RNA from the protein-deprived stem cell cultures at different points in development and used quantitative polymerase chain reaction and RNA sequencing analysis to quantify the effects of δ-catenin deprivation.  Additionally, iCRISPR genetic engineering was implemented to obtain homozygous mutant mice with high knockdown of the δ-catenin gene. Cells from these mice mutants with knocked down δ-catenin expression, in addition to cells from the human and mouse knockdown cultures, will be plated onto multi-electrode arrays to determine the consequences of insufficient δ-catenin on neural networks. We expect that δ-catenin will play a minor role in both undifferentiated human stem cells and mouse primary cells, but will significantly impact how those cells survive and mature into neurons. Ultimately, communication between neurons should be mitigated in human and mouse cell lines with knocked-down δ-catenin expression.

UC Santa Barbara Center for Science and Engineering Partnerships UCSB California NanoSystems Institute