Development of ependymal cells and their common origin with adult neural stem cells

The ventricular-subventricular zone is a neural stem cell niche located in the walls of the lateral ventricles in adult mammals. This niche contains the adult neural stem cells (B1 cells) and ependymal cells (E1 cells). These two cell types become organized during development into rosette-like structures called pinwheels. B1 cells and E1 cells are derived during development from radial glia (RG) cells. However, it is not known how pinwheels became organized and whether single RG can produce B1 and E1 cells.

We investigated how B1 and E1 cells arise during the development of the lateral wall of the lateral ventricle. We measured the apical area of RG and found that it increased dramatically during embryonic and postnatal development. After postnatal day 7, two populations of cells with different apical surfaces became evident: Whereas some cells had small apical surfaces with a single cilia, expressed VCAM and GFAP (B1 cells), others had a large apical surface and expressed FoxJ1 (E1 cells).

We next investigated if individual RG, gave rise to both E1 and B1 cells, or whether separate progenitors RG exist for E1 and B1 cells. We used a library of retroviruses with unique sequences, to distinguish the progenies of individual RG. We found clones containing both E1 cells and OB neurons, suggesting that E1 cells and B1 cells, that generate the OB neurons, were derived from a common progenitor. To further confirm this observation, we performed lineage tracing of RG cells using the Nestin::CreER;Ai14 mice. Clones of E1 and B1 cells were observed. We confirmed that B1-E1 clones were derived from embryonic progenitors that divided during mid-fetal development using BrdU. We conclude that RG cells that divide during development can give rise to B1 cells and E1 cells. This division occurs before the apical expansion that results in the formation of pinwheels.

• Nombre: José Ignacio Parraguez García
• Laboratorio: Brain Tumor Research Center
• Mención: Biología Celular y Molecular
• Director Tesis: Arturo Alvarez-Buylla