Fine structure of initial outgrowth of processes induced in a pheochromocytoma cell line (PC12) by nerve growth factor

Abstract

Cells of the PC12 line (which is derived froma rat pheochromocytoma) develop neuron-like processes upon exposure to nerve growth factor (NGF), and thus provide an opportunity to study this phenomenon de novo. We have used the transmission electron microscope to analyse the early stages of process outgrowth (1, 2, 3 and 7 days) to determine what organelles are involved and in what sequence they appear during development. Despite the non-synchronous response to NGF, we can derive three main stages in early process formation. (1) NGF-treated cells develop conical extensions similar to, but larger and more numerous than those of controls. Extensions terminate in bulbous expansions that contain large number of chromaffin-like granules and bear microspikes filled with microfilaments. (2) The extensions of NGF-treated cells then acquire membranous organelles indicative of transmitter packaging and/or recycling of cytoplasmic membranes, for example, tubular reticulum, clear and dense-cored vesicles, multivesicular bodies, and lysosomes. (3) As processes elongate, they develop a shaft that contains an array of microtubules and fine tubular reticulum dispersed in a filamentous matrix, and varicosities that exhibit the same organelles seen in stage 2. The discussion stresses the similarities in the outgrowth of processes in PC12 cells and neurons, and speculates that NGF causes a change in organization and/or quantity or organelles that already exist in non-treated control cells.