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Pax6-induced alteration of cell fate: shape changes, expression of neuronal alpha tubulin, postmitotic phenotype, and cell migration |
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Published in | Journal of neurobiology. 2006, vol. 66, no. 5, p. 421-436 | |
Abstract | The transcription factor Pax6 plays an important role in the development of the central nervous system. To understand its mechanism of action, we transduced HeLa cells with a Pax6-expressing lentiviral vector. Upon transduction, HeLa cells markedly changed shape and formed neuritelike extensions. Pax6-transduced HeLa cells expressed high levels of neuronal alpha3 tubulin, demonstrating a partial transdifferentiation towards a neuronal phenotype. Neurons are postmitotic cells. Pax6-transduced HeLa cells became postmitotic through mechanisms involving up-regulation of p53 and cyclin-dependent kinase inhibitor p21. One of the most striking effects of Pax6 was observed by time-lapse videomicroscopy: cells started to dissociate from cell clusters and displayed intense migratory activity. Migration was accompanied by dynamic and reversible shape changes. Our results identified three elements of Pax6 action: (i) expression of neuron-specific genes; (ii) establishment of a postmitotic phenotype; and (iii) involvement in the regulation of cell shape and cell migration. | |
Keywords | Animals — Cell Cycle/physiology — Cell Differentiation/ physiology — Cell Division/physiology — Cell Lineage/physiology — Cell Movement/ physiology — Cell Shape/physiology — Cells, Cultured — Central Nervous System/cytology/ embryology/metabolism — Cyclin-Dependent Kinase Inhibitor p21/metabolism — Eye Proteins/genetics/ metabolism — Hela Cells — Homeodomain Proteins/genetics/ metabolism — Humans — Mice — Neurites/metabolism/ultrastructure — Neurons/cytology/ metabolism — Paired Box Transcription Factors/genetics/ metabolism — Phenotype — Repressor Proteins/genetics/ metabolism — Transduction, Genetic — Tubulin/ metabolism — Tumor Suppressor Protein p53/metabolism | |
Identifiers | DOI: 10.1002/neu.20225 PMID: 16425216 | |
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Citation (ISO format) | CARTIER, Laetitia et al. Pax6-induced alteration of cell fate: shape changes, expression of neuronal alpha tubulin, postmitotic phenotype, and cell migration. In: Journal of neurobiology, 2006, vol. 66, n° 5, p. 421-436. doi: 10.1002/neu.20225 https://archive-ouverte.unige.ch/unige:11180 |