Phenotypic and functional characterization of adult brain neuropoiesis

Departments of ^*Neuroscience and ^§Neurosurgery, University of Florida, McKnight Brain Institute, Gainesville, FL 32610; and ^¶Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Communicated by Darwin J. Prockop, Tulane University, New Orleans, LA, May 12, 2005 (received for review January 18, 2005)

Abstract

The modern concept of neurogenesis in the adult brain is predicated on the premise that multipotent glial cells give rise to new neurons throughout life. Although extensive evidence exists indicating that this is the case, the transition from glial to neuronal phenotype remains poorly understood. A unique monolayer cell-culture system was developed to induce, expose, and recapitulate the entire developmental series of events of subventricular zone (SVZ) neurogenesis. We show here, using immunophentoypic, ultrastructural, electrophysiological, and time-lapse analyses, that SVZ-derived glial fibrillary acidic protein^low/A2B5⁺/nestin⁺ candidate founder cells undergo metamorphosis to eventually generate large numbers of fully differentiated interneuron phenotypes. A model of postnatal neurogenesis is considered in light of known embryonic events and reveals a limited developmental potential of SVZ stem/progenitor cells, whereby ancestral cells in both embryonic and postnatal/adult settings give rise to glia and GABAergic interneurons.

Footnotes

↵ ∥ To whom correspondence should be addressed at: McKnight Brain Institute, Program in Stem Cell Biology and Regenerative Medicine, University of Florida College of Medicine, 100 South Newell Drive, P.O. Box 100244, Gainesville, FL 32610. E-mail: steindler{at}mbi.ufl.edu.
↵ † B.S. and N.M.W. contributed equally to this work.
↵ ‡ D.A.S. and B.S. are involved with a biotechnology start-up company, RegenMed, Inc., which researches stem cell technology related to human therapeutics.
Author contributions: B.S., A.K.G., and D.A.S. designed research; B.S., N.M.W., D.D.L., and A.K.G. performed research; G.E. contributed new reagents/analytic tools; B.S., N.M.W., and S.N.R. analyzed data; and B.S. and D.A.S. wrote the paper.
Abbreviations: GFAP, glial fibrillary acidic protein; NS, neurospheres; P8, postnatal day 8; PSA-NCAM, polysialylated neural cell adhesion molecule; SVZ, subventricular zone.
Freely available online through the PNAS open access option.