Phenotypic and functional characterization of adult brain neuropoiesis.
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 immunophenotypic, 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.
Scheffler
Bjorn
B
Departments of Neuroscience and Neurosurgery, University of Florida, McKnight Brain Institute, Gainesville, FL 32610, USA.
Walton
Noah M
NM
Lin
Dean D
DD
Goetz
A Katrin
AK
Enikolopov
Grigori
G
Roper
Steve N
SN
Steindler
Dennis A
DA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000378:metabolism*; D004594:Electrophysiology; D018682:GABA Agents / Q000378:metabolism; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008959:Models, Neurological; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors
D018682:GABA Agents