Ank3-Dependent SVZ Niche Assembly Is Required for the Continued Production of New Neurons

SummaryThe rodent subventricular/subependymal zone (SVZ/SEZ) houses neural stem cells (NSCs) that generate olfactory bulb interneurons. It is unclear how the SVZ environment sustains neuronal production into adulthood. We discovered that the adapter molecule Ankyrin-3 (Ank3) is specifically upregulated in ventricular progenitors destined to become ependymal cells, but not in NSCs, and is required for SVZ niche assembly through progenitor lateral adhesion. Furthermore, we found that Ank3 expression is controlled by Foxj1, a transcriptional regulator of multicilia formation, and genetic deletion of this pathway led to complete loss of SVZ niche structure. Interestingly, radial glia continued to transition into postnatal NSCs without this niche. However, inducible deletion of Foxj1-Ank3 from mature SVZ ependyma resulted in dramatic depletion of neurogenesis. Targeting a pathway regulating ependymal organization/assembly and showing its requirement for new neuron production, our results have important implications for environmental control of adult neurogenesis and harvesting NSCs for replacement therapy.

► Mature ependymal niche is required for continued SVZ neurogenesis in the adult brain
► Ank3 is specifically expressed in SVZ ependymal niche cells, but not in adult NSCs
► Foxj1 turns on Ank3 in postnatal progenitors to assemble mature SVZ neurogenic niche
► Ependymal niche formation is not required for radial glial transition to adult NSCs