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

J Neurobiol. 2006 Apr;66(5):421-36. doi: 10.1002/neu.20225.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • HeLa Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Neurites / metabolism
  • Neurites / ultrastructure
  • Neurons / cytology
  • Neurons / metabolism*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Phenotype
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transduction, Genetic
  • Tubulin / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Tubulin
  • Tumor Suppressor Protein p53