Expression of the neural specific protein, GAP-43, dramatically lengthens the cell cycle in fibroblasts.

It has been demonstrated that during neurogenesis in the mammalian brain, cell-cycle lengthening in neuronal progenitors may cause them to switch from proliferation to neuron-generating division. However, little is known about the cellular mechanisms involved in lengthening of the cell cycle. Growth-associated protein-43 (GAP-43) is a nervous system-specific protein whose expression in proliferating neuroblasts is related to neurogenesis. In this study, we investigated the effect of GAP-43 on cell-cycle progression in transgenic fibroblast cells. Using cumulative bromodeoxyuridine labeling, cell-cycle kinetics in GAP-43-transgenic and control NIH 3T3 cells were analyzed. Our data demonstrate that expression of GAP-43 in fibroblasts results in lengthening of the cell cycle compared to control fibroblasts. The mechanism by which GAP-43 mediated this effect appeared to involve increasing the time spent by the cells in the G(1) phase of the cell cycle.