Musashi1: An evolutionally conserved marker for CNS progenitor cells including neural stem cells

In situ detection of neural progenitor cells including stem-like cells is e ssential for studying the basic mechanisms of the generation of cellular di versity in the CNS, upon which therapeutic treatments for CNS injuries, deg enerative diseases, and brain tumors may be based. We have generated rat mo noclonal antibodies (Mab 14H1 and 14B8) that recognize an RNA-binding prote in Musashi1, but not a Musashi1-related protein, Musashi2. The amino acid s equences at the epitope sites of these anti-Musashi1 Mabs are remarkably co nserved among the human, mouse, and Xenopus proteins. Spatiotemporal patter ns of Musashi1 immunoreactivity in the developing and/or adult CNS tissues of frogs, birds, rodents, and humans indicated that our anti-Musashi1 Mabs reacted with undifferentiated, proliferative cells in nostaining of embryon ic mouse brain cells in monolayer cultures demonstrated strong Musashi1 exp ression in Nestin(+)/RC2(+) cells. The relative number of Musashi1(+)/Nesti n(+)/RC2(+) cells increased fivefold when embryonic forebrain cells were cu ltured to form 'neurospheres' in which stem-like cells are known to be enri ched through their self-renewing mode of growth. Nestin(+)/RC2(-) cells, wh ich included T alpha 1-GFP(+) neuronal progenitor cells and GLAST(+) astrog lial precursor cells, were also Musashi1(+), as were GFAP(+) astrocytes. Yo ung neurons showed a trace of Musashi1 expression. Cells committed to the o ligodendroglial lineage were Musashi(-). Musashi1 was localized to the peri karya of CNS stem-like cells and non-oligodendroglial progenitor cells with out shifting to cell processes or endfeet, and is therefore advantageous fo r identifying each cell and counting cells in situ. Copyright (C) 2000 S. K arger AG, Basel.