Fibroblast Growth Factor-2 Activates a Latent Neurogenic Program in Neural Stem Cells from Diverse Regions of the Adult CNS

TLDR

Neural stem cells generate neurons and glia during development, and although neurogenesis largely stops at birth, it persists in the adult subventricular zone and hippocampal dentate gyrus. The study demonstrates that adult brain precursors normally restricted to glial fate can be induced to generate neurons by FGF‑2 in vitro. FGF‑2 activates a latent neurogenic program in multipotent precursors from hippocampus, neocortex, and optic nerve, enabling them to proliferate and differentiate into neurons.

Abstract

During development of the mammalian brain, both neurons and glia are generated from multipotent neural stem cells. Although neurogenesis ceases in most areas at birth, stem cells continue to generate neurons within the subventricular zone and hippocampal dentate gyrus throughout adult life. In this work, we provide the first demonstration that precursors native to regions of the adult brain that generate only glia can also generate neurons after exposure to FGF-2 in vitro . When progenitors isolated from hippocampal tissue were directly compared with cells isolated from the neocortex , both populations were able to initiate a program of proliferative neurogenesis. Genetic marking and lineage analysis showed that a majority of the cells able to generate neurons were multipotent precursors; however, progeny from these precursors acquired the competence to differentiate into neurons only after exposure to FGF-2. The recruitment of similar FGF-2-responsive cells from the adult optic nerve, a structure well isolated from the neurogenic zones within the brain, confirmed that neuron-competent precursors naturally exist in widely divergent tissues of the adult brain.