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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. CONCLUSION 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.

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Metadaten
Document Type:Article
Language:English
Author:Francesca Orso, Richard Jäger, Raffaele Adolfo Calogero, Hubert Schorle, Piero Sismondi, Michele de Bortoli, Daniela Taverna
Parent Title (English):BMC Biology
Volume:7
First Page:25
ISSN:1741-7007
DOI:https://doi.org/10.1186/1741-7007-7-25
PMID:https://pubmed.ncbi.nlm.nih.gov/19463168
Publisher:BioMed Central
Date of first publication:2009/05/22
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2018/07/14