The rat pheochromocytoma cell line (PC12) is an extensively used model to study neuronal differentiation. The initial signaling cascades triggered by nerve growth factor (NGF) stimulation have been subject to thorough investigation and are well characterized. However, knowledge of temporal transcriptomal regulation during NGF-induced differentiation of PC12 cells remains far from complete. We performed a microarray study that characterized temporal and functional changes of the transcriptome during 4 subsequent days of differentiation of Neuroscreen-1 PC12 cells. By analyzing the transcription profiles of 1595 NGF-regulated genes, we show a large diversity of transcriptional regulation in time. Also, we quantitatively identified 26 out of 243 predefined biological process and 30 out of 255 predefined molecular function classes that are specifically regulated by NGF. Combining the temporal and functional transcriptomal data revealed that NGF selectively exerts a temporally coordinated regulation of genes implicated in protein biosynthesis, intracellular signaling, cell structure, chromatin packaging and remodeling, intracellular protein traffic, mRNA transcription, and cell cycle. We will discuss how NGF-induced changes may modulate the transcriptional response to NGF itself during differentiation.
J. Neurochem. (2008) 105, 2388–2403.