AP-2α regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase
1 Molecular Biotechnology Center, University of Torino, via Nizza, 52, 10126, Torino, Italy
2 Department of Oncological Sciences, University of Torino, SP142, 10060, Candiolo, Italy
3 Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany
4 Bioinformatics and Genomics Unit, Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Torino, Italy
5 Institute for Cancer Research and Treatment (IRCC), SP 142, 10060 Candiolo (To), Italy
6 Center for Complex Systems in Molecular Biology and Medicine, University of Torino, Torino, Italy
BMC Biology 2009, 7:25 doi:10.1186/1741-7007-7-25Published: 22 May 2009
Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α 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.
We down-modulated AP-2α 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-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme.
We show that AP-2α plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2α regulated gene Axl is an essential player in GN-11 neuron migration.