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Unformatted text preview: Neurogenesis in Adult Subventricular Zone Arturo Alvarez-Buylla 1 and Jose Manuel Garca-Verdugo 2 1 Department of Neurological Surgery, Brain Tumor Research Center, San Francisco, California 94143-0520, and 2 Department of Cellular Biology, Faculty of Biology, University of Valencia, Valencia, Spain 46100 Much excitement has been generated by the identification of adult brain regions harboring neural stem cells and their con- tinual generation of new neurons throughout life. This is an important departure from traditional views of the germinal po- tential of the postnatal brain. However, a more profound para- digm shift may be emerging. Studies of adult neurogenesis in the subventricular zone (SVZ) have revealed unexpected prop- erties of neuronal progenitors and new mechanisms of neuronal migration. Here we discuss some recent findings that examine the origin, migration, and function of SVZ-derived new neurons in adult brain and highlight areas that offer exiting opportunities for future research. Along much of the lateral walls of the lateral ventricles lies the largest germinal zone of the adult mammalian brain, the SVZ (Doetsch and Alvarez-Buylla, 1996). In fully adult mammals, mew neurons born in the SVZ of adults migrate anteriorly into the olfactory bulb (OB), where they mature into local interneu- rons (Altman, 1969; Lois and Alvarez-Buylla, 1994; Kornack and Rakic, 2001; Pencea et al., 2001a) (Fig. 1). SVZ neural stem cells can be grown in culture with epidermal growth factor (EGF), fibroblast growth factor (FGF), or the two combined (Weiss et al., 1996; Temple and Alvarez-Buylla, 1999; Gage, 2000). As such, the SVZ represents an important reservoir of progenitors in the adult brain, perhaps harboring cell populations that could be used for neuroregenerative therapy. These findings dramatically change the way we think about the adult brain. However, a deeper paradigm shift may be emerging as these discoveries raised basic mechanistic questions not easily explained by classical views of brain development. (1) Which cells give rise to new neurons in adult brain, and how is the production of these new neurons regulated? (2) How do the young neurons move through adult brain and find their way into the OB? (3) What is the function of neuronal replacement in the adult OB? Two decades ago, it was difficult to imagine that neurogenesis and neuronal migration could be studied in adult brain. However, the SVZOB system has become an attractive experimental model in which to study neural stem cells, neuro- genesis, the migration of young neurons, and their differentiation and death. Moreover, the entire process raises basic questions about how neural circuits benefit from a constant exchange of neurons....
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- Winter '08