VEGF stimulates neurogenesis in vitro and in vivo. VEGF, an angiogenic protein with neurotrophic and neuroprotective effects, was shown to promote the proliferation of neuronal precursors in murine cerebral cortical cultures and in adult rat brain. VEGF (>10 ng/ml) increased BrdUrd incorporation into cells expressing immature neuronal markers and increased cell numbers by 20–30%. Cultured cells labeled by BrdUrd expressed VEGFR2/Flk-1 but not VEGFR1/Flt-1, and the effect of VEGF was blocked by the VEGFR2/Flk-1 inhibitor SU1498. Intracerebroventricular administration of VEGF increased BrdUrd labeling in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 colocalized with the immature neuronal marker doublecortin (Dcx). The increase in BrdUrd labeling was due to increased cell proliferation, not decreased cell death. Cells labeled with BrdUrd after VEGF treatment included immature and mature neurons, astroglia, and endothelial cells. These findings suggest that VEGF is involved in neurogenesis. VEGF is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. Recent evidence indicates that VEGF can also act directly on neurons to produce neurotrophic and neuroprotective effects. VEGF stimulates axonal outgrowth and improves the survival of cultured superior cervical and dorsal root ganglion neurons, enhances the survival of mesencephalic neurons in organotypic explant cultures, protects HN33 cells from death induced by serum withdrawal, reduces hypoxic death of HN33 cells and cultured cerebral cortical neurons, and protects cultured hippocampal neurons from glutamate toxicity. Conversely, inhibition of VEGF signaling leads to apoptosis in cortical neuron cultures, and deletion of the hypoxia-response element from the VEGF promoter causes motor-neuron degeneration in mice. Neurogenesis persists in discrete regions of the adult brain, including the rostral subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). VEGF receptor Flk-1 is expressed in neural progenitor cells of the mouse retina, and its activation stimulates their differentiation into amacrine neurons and photoreceptor cells. Neurogenesis in the adult SGZ occurs in intimate association with angiogenesis, suggesting that common factors, such as VEGF, might be involved in both processes. To investigate whether VEGF is a neurogenic as well as an angiogenic factor, the study used the cell-proliferation markerVEGF stimulates neurogenesis in vitro and in vivo. VEGF, an angiogenic protein with neurotrophic and neuroprotective effects, was shown to promote the proliferation of neuronal precursors in murine cerebral cortical cultures and in adult rat brain. VEGF (>10 ng/ml) increased BrdUrd incorporation into cells expressing immature neuronal markers and increased cell numbers by 20–30%. Cultured cells labeled by BrdUrd expressed VEGFR2/Flk-1 but not VEGFR1/Flt-1, and the effect of VEGF was blocked by the VEGFR2/Flk-1 inhibitor SU1498. Intracerebroventricular administration of VEGF increased BrdUrd labeling in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 colocalized with the immature neuronal marker doublecortin (Dcx). The increase in BrdUrd labeling was due to increased cell proliferation, not decreased cell death. Cells labeled with BrdUrd after VEGF treatment included immature and mature neurons, astroglia, and endothelial cells. These findings suggest that VEGF is involved in neurogenesis. VEGF is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. Recent evidence indicates that VEGF can also act directly on neurons to produce neurotrophic and neuroprotective effects. VEGF stimulates axonal outgrowth and improves the survival of cultured superior cervical and dorsal root ganglion neurons, enhances the survival of mesencephalic neurons in organotypic explant cultures, protects HN33 cells from death induced by serum withdrawal, reduces hypoxic death of HN33 cells and cultured cerebral cortical neurons, and protects cultured hippocampal neurons from glutamate toxicity. Conversely, inhibition of VEGF signaling leads to apoptosis in cortical neuron cultures, and deletion of the hypoxia-response element from the VEGF promoter causes motor-neuron degeneration in mice. Neurogenesis persists in discrete regions of the adult brain, including the rostral subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). VEGF receptor Flk-1 is expressed in neural progenitor cells of the mouse retina, and its activation stimulates their differentiation into amacrine neurons and photoreceptor cells. Neurogenesis in the adult SGZ occurs in intimate association with angiogenesis, suggesting that common factors, such as VEGF, might be involved in both processes. To investigate whether VEGF is a neurogenic as well as an angiogenic factor, the study used the cell-proliferation marker