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

Abstract

Summary: 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. : Shan et al. report that matrix metalloproteinase 12 (MMP12) is required for the appropriate development of the V-SVZ neural stem cell niche, with secreted MMP12 promoting niche organization and function, including the regulation of neural stem cell quiescence. An unexpected intracellular pool of a truncated yet functional MMP12 was also identified, which has a distinct role in promoting ependymal ciliogenesis. Keywords: neural stem cell niche, ependymal cell, matrix metalloproteinase, ventricular-subventricular zone, V-SVZ