Beta amyloid protein precursor-like (Appl) is a Ras1/MAPK-regulated gene required for axonal targeting in Drosophila photoreceptor neurons
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- dc.contributor.author Mora-Sitja, Nataliaca
- dc.contributor.author Almudi, Isabelca
- dc.contributor.author Alsina i Español, Bertaca
- dc.contributor.author Corominas Guiu, Montserratca
- dc.contributor.author Serras Rigalt, Florencica
- dc.date.accessioned 2015-12-02T14:49:02Z
- dc.date.available 2015-12-02T14:49:02Z
- dc.date.issued 2013
- dc.description.abstract In a genome-wide expression profile search for genes required for Drosophila R7 photoreceptor development we found Beta amyloid protein precursor-like (Appl), the ortholog of human APP, which is a key factor in the pathogenesis of Alzheimer's disease. We analyzed Appl expression in the eye imaginal disc and found that is highly accumulated in R7 photoreceptor cells. The R7 photoreceptor is responsible for UV light detection. To explore the link between high expression of Appl and R7 function, we have analyzed Appl null mutants and found reduced preference for UV light, probably because of mistargeted R7 axons. Moreover, axon mistargeting and inappropriate light discrimination are enhanced in combination with neurotactin mutants. R7 differentiation is triggered by the inductive interaction between R8 and R7 precursors, which results in a burst of Ras1/MAPK, activated by the tyrosine kinase receptor Sevenless. Therefore, we examined whether Ras1/MAPK is responsible for the high Appl expression. Inhibition of Ras1 signaling leads to reduced Appl expression, whereas constitutive activation drives ectopic Appl expression. We show that Appl is directly regulated by the Ras/MAPK pathway through a mechanism mediated by PntP2, an ETS transcription factor that specifically binds ETS sites in the Appl regulatory region. We also found that zebrafish appb expression increased after ectopic fgfr activation in the neural tube of zebrafish embryos, suggesting a conserved regulatory mechanism.ca
- dc.description.sponsorship This work was supported by an FPU grant of the Ministerio de Educación y Ciencia, Spain to N.M.; and by the Ministerio de Ciencia e Innovació [grant numbers BFU2009-09781 and CSD2007-00008 to F.S.]
- dc.format.mimetype application/pdfca
- dc.identifier.citation Mora N, Almudi I, Alsina B, Corominas M, Serras F. Beta amyloid protein precursor-like (Appl) is a Ras1/MAPK-regulated gene required for axonal targeting in Drosophila photoreceptor neurons. Journal of cell science. 2013;126(Pt 1):536-59. DOI: 10.1242/jcs.114785ca
- dc.identifier.doi http://dx.doi.org/10.1242/jcs.114785
- dc.identifier.issn 0021-9533
- dc.identifier.uri http://hdl.handle.net/10230/25310
- dc.language.iso engca
- dc.publisher Company of Biologistsca
- dc.relation.ispartof Journal of cell science. 2013;126(Pt 1):536-59
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-09781
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2007-00008
- dc.rights Company of Biologists http://jcs.biologists.org/content/joces/126/1/53.full.pdf DOI 10.1242/jcs.114785ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.keyword Appl
- dc.subject.keyword ETS binding site
- dc.subject.keyword Axon targeting
- dc.subject.keyword Photoreceptor
- dc.subject.keyword Ras
- dc.subject.other Drosòfila -- Genèticaca
- dc.subject.other Proteïnes de la sangca
- dc.title Beta amyloid protein precursor-like (Appl) is a Ras1/MAPK-regulated gene required for axonal targeting in Drosophila photoreceptor neuronsen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca