Accelerated Differentiation in Response to Retinoic Acid After Retrovirally Mediated Gene Transfer of GAP-43 into Mouse Neuroblastoma Cells

Although substantial evidence exists for the involvement of growth‐associated protein‐43 (GAP‐43) in neuronal development and regeneration, the precise role of this protein in neurite outgrowth is currently debated. To investigate the role of GAP‐43 in the initiation of neurite outgrowth, we transfected a full‐length cDNA coding for GAP‐43 into a mouse neuroblastoma cell line (Neuro‐2a) which can be differentiated to a neuronal phenotype using retinoic acid (RA). We show that the consequent overexpression of GAP‐43 results in a change in the basic morphology of these cells, but is not in itself sufficient to induce the extension of neurites. However, overexpression of GAP‐43 results in a marked acceleration of neurite formation in response to RA. We propose that while GAP‐43 does not trigger the initiation of neurite extension, its expression is rate‐limiting for neurite outgrowth in response to differentiation agents such as RA.