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Pax6-induced alteration of cell fate: shape changes, expression of neuronal alpha tubulin, postmitotic phenotype, and cell migration

Cartier, Laetitia
Laforge, Terese
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 AnimalsCell Cycle/physiologyCell Differentiation/ physiologyCell Division/physiologyCell Lineage/physiologyCell Movement/ physiologyCell Shape/physiologyCells, CulturedCentral Nervous System/cytology/ embryology/metabolismCyclin-Dependent Kinase Inhibitor p21/metabolismEye Proteins/genetics/ metabolismHela CellsHomeodomain Proteins/genetics/ metabolismHumansMiceNeurites/metabolism/ultrastructureNeurons/cytology/ metabolismPaired Box Transcription Factors/genetics/ metabolismPhenotypeRepressor Proteins/genetics/ metabolismTransduction, GeneticTubulin/ metabolismTumor Suppressor Protein p53/metabolism
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PMID: 16425216
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