"Understanding the Vulnerability of the Developing Human Neural System: A Stem Cell Approach"
There is overwhelming evidence that environmental factors play a role in the development and progression of a host of central nervous system disorders. It is likely that many of these effects are due to insults and exposures that occur during development. Data from human exposures reveal critical windows of susceptibility (WOS) during neural development. Unfortunately, animal models fail to faithfully recapitulate these vulnerable windows creating a need for appropriate human-based model systems. We are focusing on three specific windows of neurulation susceptibility: 1) starting with human embryonic stem cells (preneurulation stage) extending to what is believed to be the first definable early in vitro neurulation stage, neural rosette formation. 2) neural rosette to neuroepithelial cell (neural tube) and 3) neural tube neuroepithelial cell to early neuronal cell differentiation. Previously we have demonstrated that using unique culture conditions in vitro sourced and uniformly generated cells corresponding to these stages were derived from human ES cells and staged cells are cryopreservable to facilitate the study of WOS during neurulation. Furthermore, the experimental paradigms could provide the foundation for additional studies that could influence FDA and EPA regulatory decision-making.