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The Journal of Neuroscience, March 15, 2002, 22(6):2255-2264
Lack of the Cell-Cycle Inhibitor p27Kip1 Results in Selective Increase of Transit-Amplifying Cells for Adult Neurogenesis
Fiona Doetsch1, 2, José Manuel-Garcia Verdugo3, Isabelle Caille2, Arturo Alvarez-Buylla2, Moses V. Chao4, and Patrizia Casaccia-Bonnefil5 1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, 2 Rockefeller University, New York, New York 10021, 3 Department of Cellular Biology, University of Valencia, Valencia 46100, Spain, 4 Molecular Neurobiology Program, Skirball Institute, New York University, New York, New York 10016, and 5 Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854
The subventricular zone (SVZ) is the largest germinal layer in the adult mammalian brain and comprises stem cells, transit-amplifying progenitors, and committed neuroblasts. Although the SVZ contains the highest concentration of dividing cells in the adult brain, the intracellular mechanisms controlling their proliferation have not been elucidated. We show here that loss of the cyclin-dependent kinase inhibitor p27Kip1 has very specific effects on a population of CNS progenitors responsible for adult neurogenesis. Using bromodeoxyuridine and [3H]thymidine incorporation to label cells in S phase and cell-specific markers and electron microscopy to identify distinct cell types, we compared the SVZ structure and proliferation characteristics of wild-type and p27Kip1-null mice. Loss of p27Kip1 had no effect on the number of stem cells but selectively increased the number of the transit-amplifying progenitors concomitantly with a reduction in the number of neuroblasts. We conclude that cell-cycle regulation of SVZ adult progenitors is remarkably cell-type specific, with p27Kip1 being a key regulator of the cell division of the transit-amplifying progenitors.
Key words: cell division; differentiation; neural progenitors; stem cells; CNS; proliferation
Copyright © 2002 Society for Neuroscience 0270-6474/02/2262255-10$05.00/0
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