Fractone Bulbs Derive from Ependymal Cells and Their Laminin Composition Influence the Stem Cell Niche in the Subventricular Zone

Fractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round depositsnamedbulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied, and it remains unclear whether they influence neural stem and progenitor cell formation, proliferation, and/or maintenance. To address these questions, we analyzed whole-mount preparations of the lateral ventricle of male and female mice by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin alpha 5 and alpha 2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin alpha 5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells revealed ependymal cells as the source of laminin alpha 5-containing fractone bulbs. Deletion of laminin alpha 5 from ependymal cells correlated with a 60% increase in cell proliferation, as determined by phospho-histone H3 staining, and with a selective reduction in the number of slow-dividing cells. These results indicate that fractones are a key component of the SVZ and suggest that laminin alpha 5 modulates the physiology of the neural stem cell niche.