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Abstract
The PC12 cell line is a well‑established model for studying nerve growth factor (NGF)–dependent neuronal differentiation, characterized by cell cycle exit and neurite outgrowth. This work investigates the signaling pathways and transcriptional mechanisms underlying NGF‑induced differentiation. Using pharmacological and molecular approaches, the study demonstrates that neurite outgrowth requires both ERK‑dependent and ERK‑independent pathways, including PI3K and Src family kinases, with sustained ERK activation necessary for maximal effects. The role of ERK signaling in regulating the transcription factor c‑fos is further defined, identifying specific phosphorylation events required for c‑fos stability and transactivation. Together, these findings clarify how NGF signaling coordinates intracellular pathways and gene regulation to drive neuronal differentiation in the PC12 model.