Unbiased measurements of postnatal cerebellar cortical growth interpreted quantitatively through topological constraints suggest prolonging of cell cycle time in Superficial EGL progenitors

Postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a stream‐lined sampling scheme/work‐flow to generate objective/unbiased estimates of cerebellar surface area and volume using stereological principles. Our data demonstrate that during the proliferative phase of EGL and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self‐renewal. These topological constraints indicate that during proliferative phases, migration out of the EGL is balanced by self‐renewal. Progenitor self‐renewal must therefore include mitotic events yielding either two cells in the same layer to increase surface area (b‐events) and mitotic events yielding two cells, with one cell in a superficial layer and one cell in a deeper layer (a‐events). Using a mathematical model constrained by these macroscopic observations, we were able to relate easily‐obtained global measurements of volume and surface area to the underlying cellular physiology. We used this overall method to quantify the lengthening of inter‐mitotic times for b‐events on a per‐cell basis. Similar methodology may prove useful by providing another layer of depth to the interpretation of results from stereological studies.