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The Journal of Neuroscience, January 5, 2005, 25(1):10-18; doi:10.1523/JNEUROSCI.1108-04.2005
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DEVELOPMENT/PLASTICITY/REPAIR
Adult Ependymal Cells Are Postmitotic and Are Derived from Radial Glial Cells during Embryogenesis
Nathalie Spassky,1,2 Florian T. Merkle,1 Nuria Flames,3 Anthony D. Tramontin,1 José Manuel García-Verdugo,3 andArturo Alvarez-Buylla1 1Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California San Francisco, San Francisco, California 94143, 2Biologie des Intéractions Neurones-Glie, Institut National de la Santé et de la Recherche Médicale U-495, Université Pierre et Marie Curie, Institut Fédératif de Recherche des Neurosciences, Hôpital de la Salpêtrière, 75651 Paris, France, and 3University of Valencia, Burjassot-46100, Spain
Ependymal cells on the walls of brain ventricles play essential roles in the transport of CSF and in brain homeostasis. It has been suggested that ependymal cells also function as stem cells. However, the proliferative capacity of mature ependymal cells remains controversial, and the developmental origin of these cells is not known. Using confocal or electron microscopy (EM) of adult mice that received bromodeoxyuridine (BrdU) or [3H]thymidine for several weeks, we found no evidence that ependymal cells proliferate. In contrast, ependymal cells were labeled by BrdU administration during embryonic development. The majority of them are born between embryonic day 14 (E14) and E16. Interestingly, we found that the maturation of ependymal cells and the formation of cilia occur significantly later, during the first postnatal week. We analyzed the early postnatal ventricular zone at the EM and found a subpopulation of radial glia in various stages of transformation into ependymal cells. These cells often had deuterosomes. To directly test whether radial glia give rise to ependymal cells, we used a Cre-lox recombination strategy to genetically tag radial glia in the neonatal brain and follow their progeny. We found that some radial glia in the lateral ventricular wall transform to give rise to mature ependymal cells. This work identifies the time of birth and early stages in the maturation of ependymal cells and demonstrates that these cells are derived from radial glia. Our results indicate that ependymal cells are born in the embryonic and early postnatal brain and that they do not divide after differentiation. The postmitotic nature of ependymal cells strongly suggests that these cells do not function as neural stem cells in the adult.
Key words: ependyma; radial glia; proliferation; ventricular zone; lateral ventricle; deuterosomes; cilia
Received March 25, 2004; revised November 4, 2004; accepted November 5, 2004.
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