Spatiotemporal Predictive Modeling of Stem Cell Fate in Ependymogenesis

Mouse brain development progresses via a systematically transformative and organized stem cell population found within the ventricular-subventricular zone (V-SVZ) of the brain’s ventricular system. Neuroepithelial cells and then radial glial cells (RGCs), the stem cell populations that line the ventricles, are sequentially replaced at the ventricular surface by multiciliated epithelial cells known as ependymal cells, generating an ependyma monolayer. Remaining neural stem cell (NSC) populations are relegated to the area immediately subjacent to the ependyma, but NSCs retain a thin apical process that contacts the ventricle surface and the cerebrospinal fluid (CSF). These remaining NSCs are clustered into ‘regenerative units’ of multiple NSC processes surrounded by ependymal cells, an organization referred to as ‘pinwheels.’ How this unique organization is generated is not known—it is only present along the lateral wall of the lateral ventricle, and not the medial wall. Here, I describe how ependymal cells sequentially replace RGCs at the ventricular surface and ask whether replacement occurs via asymmetric or symmetric divisions of the NSC. Collection of cellular composition data based on whole mounts of the lateral and medial walls of the lateral ventricles at embryonic day 13 (E13), postnatal day 1 (P1), P14 and P30 are used for development of an algorithm based on statistical analysis and modeling using the Markov Chain Monte Carlo method to elucidate the cell division patterns that result in a pinwheel-organized lateral wall versus a contiguous ependymal cell monolayer along the medial wall.