AP-2alpha regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase.
BACKGROUND
Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2alpha is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models.


RESULTS
We down-modulated AP-2alpha expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2alpha via the binding to one or more functional AP-2alpha binding sites present in its regulatory region. Analysis of migration in AP-2alpha null mouse embryo fibroblasts also reveals an essential role for AP-2alpha in cell movement via the activation of a distinct genetic programme.


CONCLUSIONS
We show that AP-2alpha plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2alpha regulated gene Axl is an essential player in GN-11 neuron migration.
Orso
Francesca
F
Molecular Biotechnology Center, University of Torino, via Nizza, 52, 10126, Torino, Italy. francesca.orso@unito.it
Jäger
Richard
R
Calogero
Raffaele Adolfo
RA
Schorle
Hubert
H
Sismondi
Piero
P
De Bortoli
Michele
M
Taverna
Daniela
D
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002999:Clone Cells; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D014158:Transcription, Genetic; D000094963:Axl Receptor Tyrosine Kinase
D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D050656:Transcription Factor AP-2; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase