JUN cooperates with the ETS domain protein pointed to induce photoreceptor R7 fate in the Drosophila eye

R7 photoreceptor fate in the Drosophila eye induced by the activation of the Sevenless receptor tyrosine kinase and the RAS/MAP kinase signal transduction pathway. We show that expression of a constitutively activated JUN isoform in ommatidial precursor cells is sufficient to induce R7 fate independent of upstream signals normally required for photoreceptor determination. We present evidence that JUN interacts with the ETS domain protein Pointed to promote R7 formation. This interaction is cooperative when both proteins are targeted to the same promoter and is antagonized by another ETS domain protein, YAN, a negative regulator of R7 development. Furthermore, phyllopod, a putative transcriptional target of RAS pathway activation during R7 induction, behaves as a suppressor of activated JUN. Taken together, these data suggest that JUN and Pointed act on common target genes to promote neuronal differentiation in the Drosophila eye, and that phyllopod might be such a common target.

[1]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[2]  James R. Woodgett,et al.  Phosphorylation of c-jun mediated by MAP kinases , 1991, Nature.

[3]  B. Dickson.  Nuclear factors in sevenless signalling. , 1995, Trends in genetics : TIG.

[4]  J. Piette,et al.  Induction of a factor that binds to the polyoma virus A enhancer on differentiation of embryonal carcinoma cells , 1987, Nature.

[5]  G. Rubin,et al.  Signalling by the sevenless protein tyrosine kinase is mimicked by Rasl activation , 1992, Nature.

[6]  D. Bohmann,et al.  Functional dissection of AP-1 transcription factors using the Gal4 adaptor assay. , 1992, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[7]  M. Bate,et al.  The development of Drosophila melanogaster , 1993 .

[8]  R. Ueda,et al.  pokkuri, a Drosophila gene encoding an E-26-specific (Ets) domain protein, prevents overproduction of the R7 photoreceptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Richard Treisman,et al.  Transcriptional Regulation by Extracellular signals: Mechanisms and Specificity , 1995, Cell.

[10]  Henry C. Chang,et al.  phyllopod functions in the fate determination of a subset of photoreceptors in drosophila , 1995, Cell.

[11]  G. Rubin,et al.  A putative Ras GTPase activating protein acts as a negative regulator of signaling by the Sevenless receptor tyrosine kinase , 1992, Cell.

[12]  E. Hafen,et al.  Control of drosophila photoreceptor cell fates by phyllopod, a novel nuclear protein acting downstream of the raf kinase , 1995, Cell.

[13]  G. Rubin,et al.  Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila. , 1994, Annual review of neuroscience.

[14]  E. Hafen,et al.  Raf functions downstream of Rasl in the Sevenless signal transduction pathway , 1992, Nature.

[15]  R. Tjian,et al.  The Drosophila Fos-related AP-1 protein is a developmentally regulated transcription factor. , 1990, Genes & development.

[16]  M. Karin,et al.  Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73 , 1991, Nature.

[17]  E. Hafen,et al.  A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways , 1994, Cell.

[18]  M. C. Ellis,et al.  Drosophila Jun mediates Ras-dependent photoreceptor determination , 1994, Cell.

[19]  B. Wasylyk,et al.  The collagenase gene promoter contains a TPA and oncogene‐responsive unit encompassing the PEA3 and AP‐1 binding sites. , 1990, The EMBO journal.

[20]  Gerald M. Rubin,et al.  Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein , 1992, Cell.

[21]  B. Wasylyk,et al.  The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation , 1990, Nature.

[22]  E. Hafen,et al.  Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye , 1991, Cell.

[23]  T. Hunter,et al.  The c-fos protein interacts with c-Jun AP-1 to stimulate transcription of AP-1 responsive genes , 1988, Cell.

[24]  M. Karin,et al.  Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain , 1991, Nature.

[25]  A. van der Eb,et al.  A new technique for the assay of infectivity of human adenovirus 5 DNA. , 1973, Virology.

[26]  Gerald M. Rubin,et al.  The activities of two Ets-related transcription factors required for drosophila eye development are modulated by the Ras/MAPK pathway , 1994, Cell.

[27]  W. Harris,et al.  Genetic dissection of the photoreceptor system in the compound eye of Drosophila melanogaster , 1976, The Journal of physiology.

[28]  J. Schlessinger,et al.  How receptor tyrosine kinases activate Ras. , 1993, Trends in biochemical sciences.

[29]  R. Wepf,et al.  The Drosophila orphan nuclear receptor seven-up requires the Ras pathway for its function in photoreceptor determination. , 1995, Development.

[30]  C. Klämbt,et al.  The Drosophila gene pointed encodes two ETS-like proteins which are involved in the development of the midline glial cells. , 1993, Development.

[31]  C. Marshall,et al.  MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. , 1994, Current opinion in genetics & development.

[32]  E. Hafen,et al.  Prepattern in the developing Drosophila eye revealed by an activated torso--sevenless chimeric receptor. , 1992, Genes & development.

[33]  N. Perrimon,et al.  Drosophila homolog of the mammalian jun oncogene is expressed during embryonic development and activates transcription in mammalian cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Ernst Hafen,et al.  The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway , 1994, Nature.

[35]  G. Rubin,et al.  The presumptive R7 cell of the developing Drosophila eye receives positional information independent of sevenless, boss and sina , 1992, Mechanisms of Development.

[36]  Gerald M Rubin,et al.  Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway , 1995, Cell.

[37]  D. Ready,et al.  Neuronal differentiation in Drosophila ommatidium. , 1987, Developmental biology.

[38]  B. Wasylyk,et al.  The Ets family of transcription factors. , 1993, European journal of biochemistry.

[39]  D. Bohmann,et al.  Intramolecular signal transduction in c‐Jun. , 1995, The EMBO journal.