Manta-Sphere

"One of the focuses of our lab is adult neurogenesis in which new neurons are born from a pool of stem cells and integrate into their environment as mature, active cells. There are two main regions in the adult brain where adult neurogenesis occurs, the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. These stem cells have been associated with learning and memory, brain plasticity and replacement of dying neurons. This image represents a small part of my research in which I have isolated neural stem cells from the SVZ of adult mice and cultured them in vitro. These cells grow in a sphere-like formation in vitro which is not duplicated in vivo. They have been plated onto a matrix and differentiated for 16 hours. The cells have then been stained for astrocytes in green using glial fibrillary acidic protein (GFAP), mature neurons in red using beta-III tubulin, and all nuclei in blue using DAPI.

Presenilin-1 Regulates Neural Progenitor Cell Differentiation in the Adult Brain

Presenilin-1 (PS1) is the catalytic core of the aspartyl protease γ-secretase. Previous genetic studies using germ-line deletion of PS1 and conditional knock-out mice demonstrated that PS1 plays an essential role in neuronal differentiation during neural development, but it remained unclear whether PS1 plays a similar role in neurogenesis in the adult brain. Here we show that neural progenitor cells infected with lentiviral vectors-expressing short interfering RNA (siRNA) for the exclusive knockdown of PS1 in the neurogenic microenvironments, exhibit a dramatic enhancement of cell differentiation. Infected cells differentiated into neurons, astrocytes and oligodendrocytes, suggesting that multipotentiality of neural progenitor cells is not affected by reduced levels of PS1. Neurosphere cultures treated with γ-secretase inhibitors exhibit a similar phenotype of enhanced cell differentiation, suggesting that PS1 function in neural progenitor cells is γ-secretase-dependent. Neurospheres infected with lentiviral vectors expressing siRNA for the targeting of PS1 differentiated even in the presence of the proliferation factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), suggesting that PS1 dominates EFG and bFGF signaling pathways. Reduction of PS1 expression in neural progenitor cells was accompanied by a decrease in EGF receptor and β-catenin expression level, suggesting that they are downstream essential transducers of PS1 signaling in adult neural progenitor cells. These findings suggest a physiological role for PS1 in adult neurogenesis, and a potential target for the manipulation of neural progenitor cell differentiation