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Updated: May 5, 2026
Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
Published on: March 2, 2018
Clonal variants of PC12 pheochromocytoma cells with altered response to nerve growth factor
Abstract:
We describe the isolation and characterization of clonal variants of PC12 pheochromocytoma cells which have been selected for loss of response to nerve growth factor (NGF). PC12 cells mutagenized with ethyl methanesulfonate were cultured in the presence of NGF, causing normal cells to cease proliferation and allowing the isolation of cell clones which do not show growth inhibition by NGF. Some but not all of these clones also failed to respond morphologically to NGF. Forty clones were isolated and characterized. Many exhibited altered morphologies of a variety of types, including clones with an NGF-independent formation of neurites and clones with various types of flattened epithelial morphology. Variant clones appeared to be mutants since their frequency of occurrence was increased by mutagen, the clones were generally phenotypically stable and no alteration in chromosomal composition was observed. Three clones lacked NGF receptor. Some clones responded morphologically to NGF (by forming neurites) without inhibition of proliferation. Several clones which did not otherwise respond to NGF nevertheless responded with transient membrane ruffling. Thus transient changes in cell surface morphology caused by NGF binding do not necessarily lead to subsequent responses. Several alternative hypotheses concerning the nature of the mutations induced are discussed.
Insights
Researchers isolated and characterized PC12 pheochromocytoma cell variants that lost nerve growth factor (NGF) response. These mutants provide insights into NGF signaling pathways and cellular differentiation.
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Biology
Background:
- PC12 pheochromocytoma cells are a standard model for studying neuronal differentiation.
- Nerve growth factor (NGF) is crucial for neuronal survival, growth, and differentiation.
- Understanding NGF signaling is key to developing treatments for neurological disorders.
Purpose of the Study:
- To isolate and characterize PC12 cell variants with reduced or absent responses to NGF.
- To investigate the molecular mechanisms underlying NGF signaling and cellular response.
- To identify potential targets for therapeutic intervention in neurological conditions.
Main Methods:
- PC12 cells were mutagenized using ethyl methanesulfonate.
- Cells were cultured in the presence of NGF to select for non-proliferating variants.
- Isolated clones were characterized for morphological and proliferative responses to NGF.
- NGF receptor expression and chromosomal stability were assessed.
Main Results:
- Forty clonal variants of PC12 cells with altered NGF responses were isolated.
- Some variants showed NGF-independent neurite outgrowth or flattened epithelial morphology.
- Three clones lacked the NGF receptor, while others responded morphologically but not mitotically.
- Transient membrane ruffling occurred in some unresponsive clones, indicating complex signaling.
Conclusions:
- Mutagenesis can generate PC12 cell variants with specific defects in NGF signaling.
- NGF response involves multiple pathways, as evidenced by differential effects on proliferation and morphology.
- These variants are valuable tools for dissecting the molecular basis of NGF action and neuronal plasticity.
