The Surface Proteome of Adult Neural Stem Cells in Zebrafish Unveils Long-Range Cell-Cell Connections and Age-Related Changes in Responsiveness to IGF

Abstract

Summary: In adult stem cell populations, recruitment into division is parsimonious and most cells maintain a quiescent state. How individual cells decide to enter the cell cycle and how they coordinate their activity remains an essential problem to be resolved. It is thus important to develop methods to elucidate the mechanisms of cell communication and recruitment into the cell cycle. We made use of the advantageous architecture of the adult zebrafish telencephalon to isolate the surface proteins of an intact neural stem cell (NSC) population. We identified the proteome of NSCs in young and old brains. The data revealed a group of proteins involved in filopodia, which we validated by a morphological analysis of single cells, showing apically located cellular extensions. We further identified an age-related decrease in insulin-like growth factor (IGF) receptors. Expressing IGF2b induced divisions in young brains but resulted in incomplete divisions in old brains, stressing the role of cell-intrinsic processes in stem cell behavior. : In this article, Chapouton and colleagues use the brain of the adult zebrafish to identify communication pathways in a native population of neural stem cells. They identify proteins expressed on the apical surfaces by a biotinylation technique and document the presence of filopodial extensions between cells. They further show the appearance of an abnormal mitotic response to IGF with age. Keywords: telencephalon, pallium, GFAP, radial glia, filopodia, lamellipodia, biotinylation, mass spectrometry, aging, neurogenesis, quiescence