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Abstract

Adult hippocampal neurogenesis continually produces new granule cells in the dentate gyrus. The capacity to generate new neurons throughout life is fundamentally dependent on maintaining a reservoir of neural stem cells and the integrity of the neurogenic niche. Within the niche, endothelial cells function as intermediary signaling platforms that modulate neurogenesis in response to circulating factors and bidirectional communication with adjacent neural stem cells. Adult neurogenesis decreases with age and is paralleled by vascular deterioration and cognitive decline. These changes are associated with a loss of circulating factors that have not yet been identified. Here we show loss of bone morphogenetic protein 9 (BMP9), a circulating factor required for vascular homeostasis, alters the dynamics of adult hippocampal neurogenesis. Thymidine analog pulse-labeling revealed proliferative activity is specifically decreased in Type 2a cells in Bmp9KO mice. Surprisingly, despite this loss in progenitor amplification, the number of cells successfully committed to the neuronal lineage is comparable between the two groups. In Bmp9KO mice, label retention is increased in immature neurons, suggesting reduced proliferation in Bmp9KO mice is mitigated by an increase in cell survival. In addition, we show Bmp9 is not expressed in the brain at the age neurogenesis was examined, thus precluding cell-autonomous regulation of neurogenic populations as previously reported for other BMPs. Taken together, these observations demonstrate BMP9 has a modulatory function in homeostatic neurogenesis.

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