A24: Hes3+ cells into tissues
Project leader: Dr. A. Androutsellis-Theotokis
The adult mammalian brain contains a population of cells which, when placed in culture, exhibit stem cell properties. Specifically, they can proliferate and their progeny can differentiate into neurons, astrocytes, and oligodendrocytes. These cells can be identified by expression of the transcription factor Hairy and Enhancer of Split 3 (Hes3). Immunohistochemical detection shows that Hes3+ cells are not confined to the established neurogenic zones of the adult brain (subventricular zone and dentate gyrus), but are present throughout the brain and spinal cord, including the striatum, substantia nigra, cerebral cortex and white matter. Microdissection and subsequent culture shows that Hes3+ cells from all these areas exhibit stem cell characteristics in vitro. The Hes3 gene, as well as the numbers of Hes3+ cells in vitro and in vivo, are regulated by a recently discovered signal transduction pathway that can be activated by treatment with ligands of the Notch, Tie2 and insulin receptors. In vivo, these treatments confer powerful neuronal rescue and motor skill benefits in models of Parkinson’s disease and ischemic stroke, presumably due to increased trophic support provided by the Hes3+ cells. However, nothing is known of the fate of Hes3+ cells. We are generating a tamoxifen - inducible Hes3 reporter mouse line to address the contribution of Hes3+ cells to brain tissue. Our work will uncover a new cell population that contributes to tissue formation and regeneration.