Characterizing the Slit/Robo Pathway in a Tissue-Engineered Rostral Migratory Stream

Kaila working in a lab.

Students

College

Faculty

Associate Professor of Neurosurgery & Bioengineering

Project Summary

This summer, I conducted independent research at the Cullen Laboratory for Neural Engineering in Neurotrauma. My project was entitled, "Characterizing the Slit/Robo Pathway in a Tissue-Engineered Rostral Migratory Stream". Our lab creates tissue-engineered models for nervous system pathways. My project focuses on a signaling pathway in the central nervous system: Slit/Robo signaling in the rostral migratory stream (RMS). In adult neurogenesis, immature neurons migrate along the RMS within a ribbon of astrocytes comprising the glial tube to reach end targets. However, neural regeneration is more challenging in the CNS due to the glial scar. Therefore, the RMS is a potential endogenous source to replace lost neurons.

The goal of my project was to optimize our established techniques to create a 3D micro-tissue astrocytic construct that mimics the structure of the glial tube. Our model is more relevant compared to currently available 2D and in-vivo models since the 3D structure provides high throughput screening that is faster and more inexpensive. Furthermore, we can learn from these in vitro assays to make educated decisions about in vivo experiments. By successfully replicating the RMS found in vivo, I could take steps toward characterizing the Slit/Robo pathway. Slit 1 is a diffusible protein released by neuroblasts and Robo2 is the corresponding receptor expressed on astrocytes. Kaneko et al. (2018) demonstrated that enhancement of Slit/Robo signaling between tangentially migrating neuroblasts and astrocytes increased their infiltration into a striatal lesion and improved functional recovery.

I completed the first step of this project by using immunocytochemistry to visualize Robo2 expression in TE-RMS in vitro (built using human astrocytes) and 2D astrocyte culture (also human astrocytes). Given the many benefits of redirecting neuroblast migration following aging, neurodegenerative disease, and/or brain injury, studying the Slit/Robo signaling pathway in our TE-RMS may confirm the ability of our constructs to correctly facilitate and direct migration of immature neurons.

I am studying the Biological Basis of Behavior with a language certification in American Sign Language and Deaf Studies. In the future, I would like to be a pediatrician specializing in developmental-behavioral pediatrics or neurology.  This past summer, I gained the confidence to work independently in my lab. I helped optimize the fabrication techniques to create our in vitro assays and used new immunocytochemistry, microscopy, and quantification techniques for characterization. By working in the Cullen Lab, I am more prepared to conduct independent research and analyze my data. Furthermore, as someone who hopes to become a doctor, it is important to understand the crucial role research plays in advancing the field of medicine. My lab mentors always stress the translational importance of each project. My research experience has helped me better understand how our neurotrauma research fits into the bigger picture of treating neurological diseases and I plan to apply this knowledge to a future career in medicine.