A Mathematical Model of Noggin and BMP Densities in Adult Neural Stem Cells

Abstract

New neurons are generated in the adult hippocampus throughout life by neural stem cells (NSCs) in a dynamic process responsive to external signalling cues. NSCs in the adult hippocampus divide infrequently, and it has been shown that bone morphogenetic protein (BMP) modulates their quiescence. Infusion of Noggin, a BMP antagonist, blocks this signalling. We investigate the balance of BMP and Noggin in this particular niche and qualitatively reproduce experimental results obtained and qualitatively reproduce experimental results with a one-dimensional reaction-diffusion model. We use the model to connect BMP signalling profiles with specific cellular outcomes and to determine whether the transient infusion of BMP leads to a signalling profile which can be reversed by the infusion of Noggin. Additionally, we analyse the role of diffusion in this system for generating signalling profiles with dramatically different cell-fate outcomes and show that diffusion-driven instability is not possible in our system of reactiondiffusion equations.

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“…Disrupting the cellular balance also disturbs the gliogenesis: neurogenesis balance (Capilla-Gonzalez et al, 2013). In the SVZ, transit-amplifying cells, activated astrocytes, and endothelial cells express BMP to favor gliogenesis, while ependymal cells express noggin to promote neurogenesis (Larripa and Gallegos, 2017). Increasing activation of microglia can cause an increase in BMP signaling, which has been previously found in the aged murine hippocampus to inhibit neural progenitor cell proliferation and subsequent neurogenesis (Yousef et al, 2015).…”