| dc.description.abstract | Spinal cord injury (SCI) is a form of damage to the spinal cord that dramatically impacts quality of life and can ultimately lead to severe effects such as loss of mobility and/or sensation. Neural progenitor cell (NPC) transplantation research has become a growing field of interest due to the therapeutic potential it has for SCI, as NPCs provide the foundation to generate different types of mature neurons that are then functionally and anatomically integrated into host circuitry after transplantation. That said, there are still many challenges with NPC transplantation that must be addressed before it becomes a viable treatment open to the market. One such challenge is truly understanding the mechanisms behind graft integration and formation of synaptic connections. The Dulin lab has previously demonstrated the remarkable ability of dissociated NPCs to self-assemble organized, multicellular domains resembling the native spinal cord dorsal horn. However, the mechanisms by which these accurately assembled tissue domains form in the dorsal horn has largely remained unknown. The goal of this study is to investigate the developmental mechanisms enabling the formation of these accurately assembled tissue domains. We hypothesize that signaling through the Notch/delta pathway, which normally underlies the formation of dorsal horn laminae in the intact spinal cord, also contributes to the formation of these multicellular domains in dissociated NPC grafts. To answer the research question, we obtained GFP and wildtype cells from E12.5 embryos to supply an in vivo and in vitro experiment. In vitro, 1%, 0.1%, and 0.01% dilutions of GFP to WT cells were cultured and stained with transcription factor markers. In vivo, 1% and 0.1% GFP to WT grafts were placed in the intervertebral space of 6 mice, which were then allowed to grow for 1 month. After sacrifice, sagittal sections of the cervical section of the spinal cords of the mice were obtained and stained for the same markers as the in vitro experiment. Future steps will involve determining when clustering occurs, depending on the clustering patterns of GFP to WT cells in vivo and in vitro seen in imaging. Once timing of this clustering is determined, inhibitors of Notch will be applied to determine if clustering is inhibited or not. | en |
