Tom A. Reh

tomreh@u.washington.edu
Professor, Department of Biological Structure

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I am interested in determining the mechanisms which control neuronal proliferation and differentiation during neurogenesis of the vertebrate central nervous system (CNS). The brain contains an enormous number of different types of neurons and glia and the generation of this phenotypic diversity is a central question of developmental biology; in addition, an understanding of the mechanisms by which different types of neurons are generated from precursor cells is fundamental for the development of techniques for reconstruction and repair of the damaged brain.

While the large number of different neuronal phenotypes in the brain make the study of their development difficult, the retina, a part of the CNS, contains only five basic types of neurons, and so its development can be analyzed in a more systematic manner.

Previous studies of the lineal relationships of the retinal precursors using retroviral infection or dye injections have shown that retinal neurons and glia have indeterminant lineages and that the cells of the germinal neuroepithelium are multipotent, giving rise to different neuronal and glial phenotypes up to their last cell division. Although the factors which restrict the fates of differentiating neuronal precursors to particular retinal phenotypes have not yet been identified, several lines of evidence indicate that the local microenvironment of a developing neuroblast can influence its proliferation and differentiation. These factors also appear to be developmentally regulated, since the age at which a neuro-epithelial cell differentiates determines the range of neuronal phenotypes that it can express.

This work involves studies of both developing and regenerating retina, including both in vivo and in vitro experimental approaches. Projects currently in progress include

1. clonal analysis of isolated neuronal precursors and the effects of particular growth factors and extracellular matrix components on their proliferation and expression of neuron specific genes, and
2. identification of novel genes necessary for retinal neurogenesis and cell commitment.