Val Wilson’s group studies the embryonic progenitors for the central nervous system, skeleton and muscles. This involves studying how and when they become a separate population of cells as well as how they are maintained and eventually eliminated.
Our primary objective is to understand how progenitors for the mouse anteroposterior axis are maintained over a relatively long period- about a third of mouse gestation- how they generate the axis, and how the length of the axis is regulated. In effect: we want to know why do mice have long tails (but not very, very long tails)?
Our lab has shown that part of the answer of why mice have long tails involves the maintenance of dual-fated progenitors called neuromesodermal progenitors that generate the spinal cord, backbone and muscles. These progenitors are present while the backbone is being formed, and no longer exist once the formation of the vertebrae is complete. If we are able to understand how these progenitors are regulated, we may be able to generate and maintain them in culture.
To this end, we use Epiblast Stem Cells (EpiSCs), a cell type that is very similar to cells in the early embryo that generate neuromesodermal progenitors. We have already shown that EpiSCs can differentiate to cell types similar to neuromesodermal progenitors, and are working on defining exactly how this occurs. EpiSC have many similar characteristics to human pluripotent stem cells, which means that any interesting findings in the mouse may be applicable to human cells- and may eventually be useful as clinical tools for generating spinal cord, vertebral or muscle cell types.
Finally, the process of making the anteroposterior axis involves generating very similar cell types (spinal cord, muscle, skeleton) over a long period. However these cell types, although similar, are not exactly the same at the beginning and end of axis elongation. Neck vertebrae are not exactly the same as rib vertebrae, or lower back and tail bone. This means that although these progenitors are something like a stem cell population (which can generate the same cell type over and over again), they are not exactly the same. They mature during development, and their eventual loss at the end of elongation may be key to determining how long the backbone is- will there be a short or long tail? The mechanisms that regulate this sequence are only just beginning to be elucidated. We are using a number of culture techniques to try and answer how these progenitors measure time.