IN-VIVO GROWTH-FACTOR EXPANSION OF ENDOGENOUS SUBEPENDYMAL NEURAL PRECURSOR CELL-POPULATIONS IN THE ADULT-MOUSE BRAIN

The lateral ventricle subependyma in the adult mammalian forebrain con tains both neural stem and progenitor cells. This study describes the in situ modulation of these subependymal neural precursor populations after intraventricular administration of exogenous growth factors. In vivo infusion of epidermal growth factor (EGF) into adult mouse forebr ain for 6 consecutive days resulted in a dramatic increase in the prol iferation and total number of subependymal cells and induced their mig ration away from the lateral ventricle walls into adjacent parenchyma. Immediately after EGF infusion, immunohistochemical characterization of the EGF-expanded cell population demonstrated that >95% of these ce lls were EGF receptor- and nestin-positive, whereas only 0.9% and 0.2% labeled for astrocytic and neuronal markers, respectively. Seven week s after EGF withdrawal, 25% of the cells induced to proliferate after 6 d of EGF were still detectable; 28% of these cells had differentiate d into new astrocytes and 3% into new neurons in the cortex, striatum, and septum. Newly generated oligodendrocytes were also observed. Thes e in vivo results (1) confirm the existence of EGF-responsive subepend ymal neural precursor cells in the adult mouse forebrain and (2) sugge st that EGF acts directly as a proliferation, survival, and migration factor for subependymal precursor cells to expand these populations an d promote the movement of these cells into normal brain parenchyma. Th us, in situ modulation of endogenous forebrain precursor cells represe nts a novel model for studying neural development in the adult mammali an brain and may provide insights that will achieve adult replacement of neurons and glia lost to disease or trauma.