Richardson, William D.

We study development of the vertebrate central nervous system (CNS).
All of the many different kinds of neurons and glial cells in the CNS
develop from a set of indistinguishable neural precursor ('stem') cells
in the embryonic neural tube. Stem cells at different locations
generate different subsets of neurons and glial cells. For example,
stem cells in the so-called pMN domain of the ventral spinal cord
generate motor neurons and oligodendrocytes, while stem cells located
more dorsally generate interneurons and astrocytes. How do they do
this? Concentration gradients of key extracellular molecules such as
Sonic hedgehog (Shh) establish a spatial coordinate system which allows
stem cells to map their positions in the early neutral tube. Different
levels of Shh receptor occupancy somehow dictate different programs of
gene expression and cell differentiation. We are trying to 1) map the
stem cell origins of different classes of neurons and glia in the CNS
and 2) discover the extracellular signals and intracellular signals and
transcription factors that cause the stem cells to adopt their
particular fates. We use a wide range of techniques including
transgenesis in mice and zebrafish, chick embryology, cell culture and
time-lapse microscopy.