Adult Ependymal Cells Are Postmitotic and Are Derived from Radial Glial Cells during Embryogenesis

By Nathalie Spassky, Florian Merkle, Nuria Flames, A. D. Tramontin, Jose Manuel García-Verdugo, Arturo Alvarez-Buylla. Journal of Neuroscience, 2005

718 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/04d9c251ab2c22943ebd17fc7c6eb0e22cd9e6b6

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Citations in the corpus

EphB signaling controls lineage plasticity of adult neural stem cell niche cells (2010, background): “Ependymal cells and subventricular zone astrocytes both originate from radial glial cells (Spassky et al., 2005), which act as neural stem cells in the developing central nervous system.”
Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke (2009, background): “and a final fate of radial glial cells is ependymal cell”
Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. (2006, methodology): “Postnatally, a subpopulation of radial glia gives rise to ependymal cells that form the epithelial lining of the ventricles (Spassky et al., 2005).”
The Glial Nature of Embryonic and Adult Neural Stem Cells (2009, background): “However, other studies indicated that ependymal cells do not generate neurospheres with NSC properties in vitro (Chiasson et al. 1999, Capela & Temple 2002) and that ependymal cells become postmitotic during development (Spassky et al. 2005).”
Radial glia cells are candidate stem cells of ependymoma. (2005, background): “Tumor sphere-forming ependymoma cells display a radial glia cell immunophenotype Clonally derived secondary tumor spheres generated by ependymoma and medulloblastoma stem cell-like cells after 7 days in culture express the neural progenitor cell markers Nestin and CD133.”
Brain micro-ecologies: neural stem cell niches in the adult mammalian brain (2008, background): “123 follicle and nervous system has revealed common and unique features (figure 1; reviewed in Spradling et al. 2001; Doetsch 2003b; Fuchs et al. 2004; Li & Xie 2005).”
Hedgehog Signaling in the Subventricular Zone Is Required for Both the Maintenance of Stem Cells and the Migration of Newborn Neurons (2007, background): “org as supplemental material), a glycosylphosphatidylinositolanchored membrane glycoprotein expressed in E and A cells (Calaora et al., 1996; Spassky et al., 2005).”
High Levels of Id1 Expression Define B1 Type Adult Neural Stem Cells (2009, background): “, 1999) continues to stir controversy (Capela and Temple, 2002; Chiasson et al., 1999; Doetsch et al., 1999a; Laywell et al., 2000; Spassky et al., 2005).”
Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. (2011, neutral): “Viral targeting of these cells via their radial processes, as well as anatomical studies, have demonstrated that during the next several days of postnatal development, the radial glia located on the walls of the lateral ventricles retract their long RC2-positive distal process, lose RC2 expression, ”