Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche.

ABSTRACT

The regulatory mechanisms that control neural stem cell (NSC) activation in the adult ventricular-subventricular zone (V-SVZ) stem cell niche have been the focus of intense investigation, yet how the niche first develops and organizes is poorly understood. Here, we examined matrix metalloproteinases (MMPs) for potential roles in V-SVZ stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche NSCs. Surprisingly, ependymal cells were found to have an intracellular pool of MMP12 that promoted ependymal cell ciliogenesis by upregulating FOXJ1. In addition, both extracellular and intracellular MMP12 were found to regulate V-SVZ niche output by promoting NSC quiescence. These findings reveal that extracellular and intracellular MMP12 have both unique and overlapping roles that help orchestrate the development of the adult V-SVZ stem cell niche.