Biography
Control of Cell Survival, Growth, Proliferation and Differentiation. How do developing animal cells decide whether to live or die, grow or stop growing, proliferate or stop proliferating, or to differentiate into one cell type rather than another? We have been addressing these questions mainly in the rodent nervous system (CNS), using the optic nerve, sciatic nerve, and retina as model systems. As expected, these decisions are determined by a combination of cell-cell interactions and cell-intrinsic programmes that depend on the cell's history.
In the optic nerve, we have identified a number of the molecules that control these decisions in the oligodendrocyte lineage, the cells that make myelin in the CNS. We are especially interested in the timing mechanism that stops cell division and initiates differentiation at the appropriate time in development. The timer depends on a number of intracellular proteins, whose concentrations increase or decrease progressively as the precursor cells proliferate. The levels of some of these proteins depend on transcriptional controls, while others depend on post-transcriptional controls.
We are interested in how the size of an animal or organ is determined. We have studied the factors that control the final number of olygodendrocytes in the optic nerve, and we have begun to study how cell size is controlled from both inside and outside the cell.
In the retina, multipotential precursor cells give rise to at least seven types of nerve cells and glial cells. We have developed a clonal cell culture system to study how an individual precursor cell decides which type of cell to become. We have found that asymmetrical cell divisions may contribute to cell diversification by seggregating cell fate determinants such as the Numb protein. |
