Title: Quantitative High-Throughput Screening of Human Neurodevelopment for Toxicology and Precision Medicine with RosetteArray™ Technology
Abstract: Central nervous system (CNS) development begins with formation of the neural tube, the eventual source of all brain and spinal cord tissue. Alterations in this process are well known to result in birth defects, specifically neural tube defects, like Spina bifida. More recently, subtle prenatal changes in behaviors of the cells that make up the neural tube have been linked to neurodevelopmental and even adult-onset neurodegenerative disorders. Thus, investigation of early neurodevelopment can be useful for potential treatment and prevention of many more neurologic disorders than previously realized. However, the hundreds of genetic variants linked to altered neurodevelopment coupled with the myriad potentially toxic exposures from chemicals and drugs in our everyday life make assessing neurodevelopmental risk difficult. At Neurosetta, we have designed our RosetteArray™ technology to model the first stage of CNS development, i.e., formation of the neural tube, by harnessing the ability of human pluripotent stem cells to self-organize into rosette structures that closely resemble a section of the developing CNS. We’ve demonstrated rapid and reproducible generation of single rosette tissues of standardized size and shape from multiple regions of the developing CNS (forebrain-lumbosacral spinal cord). To assess the efficacy of the RosetteArray technology to model neural development we tested the effects of common chemical and genetic causes of neural tube defects (birth defects). Further, we used the technology to perform a large chemical library screen of drugs, pesticides, and industrial chemicals to assess its fitness for screening general developmental neurotoxicity. The results of these experiments show that the RosetteArray technology is a highly repeatable and predictive tool for assessing alterations in human CNS development and an excellent complement to the battery of in vitro screening tools for assessing human neurodevelopmental toxicity.
Join Zoom Meeting
https://uwmadison.zoom.us/j/91814162149?pwd=AYgwgbFNekOLHyQrj7wUCkxem9b2Yw.1
Meeting ID: 918 1416 2149
Passcode: 970506