Research Summary
Neural stem cells and their niche in the adult mammalian brain

Stem cells residing in germinal regions in the adult brain continuously generate large numbers of neurons, which become integrated into neural circuits. In mammals, new neurons are incorporated into areas important for olfaction and for memory formation. The addition of thousands of neurons each day provides a powerful means of sculpting brain circuitry. Although the functional consequences of adult neurogenesis are not yet understood, much has been learned about their cellular lineage. We have found that the stem cells for in vivo adult neurogenesis are a subset of astrocytes, which generate neurons via an intermediate short-lived transit amplifying cell. The identification of the in vivo stem cells as astrocytes raises the exciting possibility that other brain astrocytes may be latent stem cells. Stem cell potential is not only restricted to the in vivo stem cells, the transit amplifying cells can also act as stem cells. We are using a variety of molecular, cellular and genetic approaches to discover the regulation, lineage relationships, diversity and function of stem cells and neuronal production in the adult mammalian brain. The biology of neural stem cells and their in vivo niche is key to understanding brain repair and neural pathologies, including tumors, and may also lead to insights in other stem cell fields.

Selected Publications

1. F. Doetsch (2003) The glial identity of neural stem cells. Nature Neuroscience, 6 1127-1134

2. F. Doetsch (2003) A niche for adult neural stem cells. Current Opinion in Genetics and Development, 13, 543-550

3. F. Doetsch, L. Petreanu, I. Caille, J.M. Garcia-Verdugo and A. Alvarez-Buylla (2002). EGF converts transit amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron, 36, 1021-1034

4. F. Doetsch, I. Caille, D. Lim, J.M. Garcia-Verdugo and A. Alvarez-Buylla (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716

5. F. Doetsch, J.M. Garcia-Verdugo and A. Alvarez-Buylla (1999). Regeneration of a germinal layer in the adult mammalian brain. PNAS 96, 11619-11624

6. F. Doetsch and A. Alvarez-Buylla (1996). Network of tangential pathways for neuronal migration in adult mammalian brain. PNAS 93, 14895-14900