The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

spi  -  spitz

Drosophila melanogaster

Synonyms: CG10334, CT29014, Dmel\CG10334, EP(2)2378, Protein spitz, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of spi

  • Medial fusion of denticle belts is also a hallmark of spitz group genes, yet its underlying cause is unknown [1].

High impact information on spi

  • In accordance with the putative Rhomboid active site being in the membrane bilayer, Spitz is cleaved within its transmembrane domain, and thus is, to our knowledge, the first example of a growth factor activated by regulated intramembrane proteolysis [2].
  • The polytopic membrane protein Rhomboid-1 promotes the cleavage of the membrane-anchored TGFalpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor [2].
  • Until now, the mechanism of this key signaling regulator has been obscure, but our analysis suggests that Rhomboid-1 is a novel intramembrane serine protease that directly cleaves Spitz [2].
  • Star is present throughout the secretory pathway and is required to export Spitz from the endoplasmic reticulum to the Golgi apparatus [3].
  • Twin peaks: Spitz and Argos star in patterning of the Drosophila egg [4].

Biological context of spi

  • Gene dosage studies among ventrolateral genes suggest that the rho product (Rho) may facilitate Spi-EGF-R signaling, resulting in activation of RAS [5].
  • 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 [6].
  • The DER null phenotype was distinct from that of either spitz or vein mutants, suggesting that a combination of these or other ligands was required for aspects of DER function [7].
  • Examination of mutant embryos reveals that spi is involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development [8].
  • DER expression is not terminated in the midline glia after spitz group signaling triggers changes in gene expression [9].

Anatomical context of spi


Associations of spi with chemical compounds


Physical interactions of spi


Enzymatic interactions of spi

  • Small wing PLCgamma is required for ER retention of cleaved Spitz during eye development in Drosophila [16].

Regulatory relationships of spi

  • This work demonstrates that Spitz triggers the DER signaling cascade [10].
  • Coexpression of Star promotes translocation of Spi to a compartment where Rho is present both in cells and in embryos [17].
  • Thus, Senseless promotes normal R8 differentiation by preventing the effects of autocrine stimulation by Spitz [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 [15].
  • Sal protein is expressed in the dorsal but not lateral ectoderm and acts as a competence modifier to bias the response to Spi ligand in favour of the oenocyte fate [19].

Other interactions of spi

  • In the embryo, vn is a target of Spi/DER signaling mediated by the ETS transcription factor PointedP1 (PntP1) [20].
  • The ventrolateral genes include spitz, which encodes an EGF-like ligand, and Star [5].
  • While Spi is retained in the ER, the retention of Krn is only partial [21].
  • A mechanism for adjustment to variable levels of secreted Spitz emanating from the midline may be provided by Argos, which forms an inhibitory feedback loop for DER activation [11].
  • This result indicates that sim acts upstream of all the other spi/Egfr genes [22].


  1. EGF receptor signalling protects smooth-cuticle cells from apoptosis during Drosophila ventral epidermis development. Urban, S., Brown, G., Freeman, M. Development (2004) [Pubmed]
  2. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Urban, S., Lee, J.R., Freeman, M. Cell (2001) [Pubmed]
  3. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Lee, J.R., Urban, S., Garvey, C.F., Freeman, M. Cell (2001) [Pubmed]
  4. Twin peaks: Spitz and Argos star in patterning of the Drosophila egg. Stevens, L. Cell (1998) [Pubmed]
  5. The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway. Sturtevant, M.A., Roark, M., Bier, E. Genes Dev. (1993) [Pubmed]
  6. 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]
  7. 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]
  8. The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis. Rutledge, B.J., Zhang, K., Bier, E., Jan, Y.N., Perrimon, N. Genes Dev. (1992) [Pubmed]
  9. Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos. Stemerdink, C., Jacobs, J.R. Development (1997) [Pubmed]
  10. Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Schweitzer, R., Shaharabany, M., Seger, R., Shilo, B.Z. Genes Dev. (1995) [Pubmed]
  11. The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. Golembo, M., Raz, E., Shilo, B.Z. Development (1996) [Pubmed]
  12. The Drosophila TGF alpha homolog Spitz acts in photoreceptor recruitment in the developing retina. Tio, M., Moses, K. Development (1997) [Pubmed]
  13. Palmitoylation of the EGFR ligand Spitz by Rasp increases Spitz activity by restricting its diffusion. Miura, G.I., Buglino, J., Alvarado, D., Lemmon, M.A., Resh, M.D., Treisman, J.E. Dev. Cell (2006) [Pubmed]
  14. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor. Freeman, M. Mech. Dev. (1994) [Pubmed]
  15. 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]
  16. Small wing PLCgamma is required for ER retention of cleaved Spitz during eye development in Drosophila. Schlesinger, A., Kiger, A., Perrimon, N., Shilo, B.Z. Dev. Cell (2004) [Pubmed]
  17. Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz. Tsruya, R., Schlesinger, A., Reich, A., Gabay, L., Sapir, A., Shilo, B.Z. Genes Dev. (2002) [Pubmed]
  18. Senseless represses nuclear transduction of Egfr pathway activation. Frankfort, B.J., Mardon, G. Development (2004) [Pubmed]
  19. Insect oenocytes: a model system for studying cell-fate specification by Hox genes. Gould, A.P., Elstob, P.R., Brodu, V. J. Anat. (2001) [Pubmed]
  20. Tissue-specific regulation of vein/EGF receptor signaling in Drosophila. Wessells, R.J., Grumbling, G., Donaldson, T., Wang, S.H., Simcox, A. Dev. Biol. (1999) [Pubmed]
  21. Keren, a new ligand of the Drosophila epidermal growth factor receptor, undergoes two modes of cleavage. Reich, A., Shilo, B.Z. EMBO J. (2002) [Pubmed]
  22. The hierarchical relationship among the spitz/Egfr signaling genes in cell fate determination in the Drosophila ventral neuroectoderm. Chang, J., Jeon, S.H., Kim, S.H. Mol. Cells (2003) [Pubmed]
WikiGenes - Universities