TRANSFORMING GROWTH-FACTOR-ALPHA NULL AND SENESCENT MICE SHOW DECREASED NEURAL PROGENITOR-CELL PROLIFERATION IN THE FOREBRAIN SUBEPENDYMA

The adult mammalian forebrain subependyma contains neural stem cells a nd their progeny, the constitutively proliferating progenitor cells. U sing bromodeoxyuridine labeling to detect mitotically active cells, we demonstrate that the endogenous expression of transforming growth fac tor-alpha (TGF alpha) is necessary for the full proliferation of proge nitor cells localized to the dorsolateral corner of the subependyma an d the full production of the neuronal progenitors that migrate to the olfactory bulbs. Proliferation of these progenitor cells also is dimin ished with age (in 23- to 25-months-old compared with 2- to 4-months-o ld mice), likely because of a lengthening of the cell cycle. Senescenc e or the absence of endogenous TGF alpha does not affect the numbers o f neural stem cells isolated in vitro in the presence of epidermal gro wth factor. These results suggest that endogenous TGF alpha and the ef fects of senescence may regulate the proliferation of progenitor cells in the adult subependyma, but that the number of neural stem cells is maintained throughout life.