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Gene Review

aos  -  argos

Drosophila melanogaster

Synonyms: Aos, Argos, CG4531, DmAos, Dmel\CG4531, ...
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Disease relevance of argos

  • Overactivity of EGFR signaling, as achieved by heat-shock-driven activation of a wild-type rhomboid (rho) construct, or by loss of function of argos (aos) or yan, results in an hyperplasia and deformity of the head midline structures [1].

High impact information on argos

  • Consequent high-level EGFR activation leads to localized expression of the diffusible inhibitor Argos, which alters the profile of signaling [2].
  • Twin peaks: Spitz and Argos star in patterning of the Drosophila egg [3].
  • A developmental analysis of argos mutant eyes indicates that the mystery cells, which are usually nonneuronal, are transformed into extra photoreceptors, and that supernumerary cone cells and pigment cells are also recruited [4].
  • Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif [5].
  • In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development [5].

Biological context of argos

  • Fewer midline glia enter apoptosis in embryos lacking argos function [6].
  • In this work, we assess the role of argos in the determination of midline glia cell number [6].
  • Loss-of-function mutations in components of the Ras/MAPK signaling cascade act as dominant suppressors of the phenotype caused by the argos null mutations [7].
  • These results indicate that Aos exerts its inhibitory function through dual molecular mechanisms: by blocking both the receptor dimerization and the binding of activating ligand to the receptor [8].
  • The Drosophila secreted protein Argos regulates signal transduction in the Ras/MAPK pathway [7].

Anatomical context of argos

  • In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells [9].
  • These include activation of N signaling to repress R8 specification, turning on argos expression, and recruiting photoreceptors R1-R7 [10].
  • When lambda top was expressed in all the follicle cells covering the oocyte, kek 1 and argos expression was induced in follicle cells all along the anterior/posterior axis of the egg chamber [11].
  • We have found that glial cells failed to differentiate in the larval optic lobes of argos mutants [12].

Associations of argos with chemical compounds

  • These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan [13].
  • We cloned the sty gene by P-element tagging and found that it encodes a putative secreted protein containing a cysteine-rich region similar to the epidermal growth factor (EGF) repeat [14].
  • The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases [15].

Physical interactions of argos


Regulatory relationships of argos

  • Argos inhibits epidermal growth factor receptor signalling by ligand sequestration [17].
  • The loss-of-function Star mutation (StarX155) dominantly suppressed the defects in the argos optic lobes, suggesting that these two genes act in an antagonistic fashion during optic lobe development [12].
  • Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death [18].
  • This effect could be recapitulated in a cell-based assay, where a higher molar concentration of mutant Argos was needed to inhibit Spitz-dependent dEGFR phosphorylation [16].
  • We showed that the argos transcripts are expressed transiently in the cells surrounding the Ch organ precursor and that the gene rhomboid (rho), which is involved in the regulation of the number of Ch organs, acts epistatically to argos in this event [19].

Other interactions of argos

  • Furthermore, Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER [8].
  • A loss-of-function argos mutation enhanced the overproduction of R7 neurons caused by gain-of-function alleles of Son of sevenless and Dsor1 [7].
  • The 90 degrees rotation also requires activity of planar polarity genes such as fz as well as the roulette (rlt) locus [20].
  • Epistatic analysis placed clown between argos and Ras1 [21].
  • Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos [6].

Analytical, diagnostic and therapeutic context of argos

  • The recombinant arg protein was detected in bacterial lysates by immunoblotting and exhibited a molecular mass of 145 kDa [22].


  1. EGFR signaling is required for the differentiation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head. Dumstrei, K., Nassif, C., Abboud, G., Aryai, A., Aryai, A., Hartenstein, V. Development (1998) [Pubmed]
  2. An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Wasserman, J.D., Freeman, M. Cell (1998) [Pubmed]
  3. Twin peaks: Spitz and Argos star in patterning of the Drosophila egg. Stevens, L. Cell (1998) [Pubmed]
  4. The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye. Freeman, M., Klämbt, C., Goodman, C.S., Rubin, G.M. Cell (1992) [Pubmed]
  5. Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster. Kretzschmar, D., Brunner, A., Wiersdorff, V., Pflugfelder, G.O., Heisenberg, M., Schneuwly, S. EMBO J. (1992) [Pubmed]
  6. Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos. Stemerdink, C., Jacobs, J.R. Development (1997) [Pubmed]
  7. The Drosophila secreted protein Argos regulates signal transduction in the Ras/MAPK pathway. Sawamoto, K., Okabe, M., Tanimura, T., Mikoshiba, K., Nishida, Y., Okano, H. Dev. Biol. (1996) [Pubmed]
  8. The interaction between the Drosophila secreted protein argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor. Jin, M.H., Sawamoto, K., Ito, M., Okano, H. Mol. Cell. Biol. (2000) [Pubmed]
  9. Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop. Golembo, M., Schweitzer, R., Freeman, M., Shilo, B.Z. Development (1996) [Pubmed]
  10. Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila. Lesokhin, A.M., Yu, S.Y., Katz, J., Baker, N.E. Dev. Biol. (1999) [Pubmed]
  11. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Queenan, A.M., Ghabrial, A., Schüpbach, T. Development (1997) [Pubmed]
  12. argos Is required for projection of photoreceptor axons during optic lobe development in Drosophila. Sawamoto, K., Okabe, M., Tanimura, T., Hayashi, S., Mikoshiba, K., Okano, H. Dev. Dyn. (1996) [Pubmed]
  13. EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm. Gabay, L., Scholz, H., Golembo, M., Klaes, A., Shilo, B.Z., Klämbt, C. Development (1996) [Pubmed]
  14. Regulation of Drosophila neural development by a putative secreted protein. Okano, H., Hayashi, S., Tanimura, T., Sawamoto, K., Yoshikawa, S., Watanabe, J., Iwasaki, M., Hirose, S., Mikoshiba, K., Montell, C. Differentiation (1992) [Pubmed]
  15. The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. Kruh, G.D., Perego, R., Miki, T., Aaronson, S.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  16. Argos mutants define an affinity threshold for spitz inhibition in vivo. Alvarado, D., Evans, T.A., Sharma, R., Lemmon, M.A., Duffy, J.B. J. Biol. Chem. (2006) [Pubmed]
  17. Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. Klein, D.E., Nappi, V.M., Reeves, G.T., Shvartsman, S.Y., Lemmon, M.A. Nature (2004) [Pubmed]
  18. Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway. Sawamoto, K., Taguchi, A., Hirota, Y., Yamada, C., Jin, M.H., Okano, H. Cell Death Differ. (1998) [Pubmed]
  19. The function of the Drosophila argos gene product in the development of embryonic chordotonal organs. Okabe, M., Sawamoto, K., Okano, H. Dev. Biol. (1996) [Pubmed]
  20. EGF signaling and ommatidial rotation in the Drosophila eye. Strutt, H., Strutt, D. Curr. Biol. (2003) [Pubmed]
  21. Mutations modulating the Argos-regulated signaling pathway in Drosophila eye development. Taguchi, A., Sawamoto, K., Okano, H. Genetics (2000) [Pubmed]
  22. Arg encodes a widely expressed 145 kDa protein-tyrosine kinase. Perego, R., Ron, D., Kruh, G.D. Oncogene (1991) [Pubmed]
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