Gene Symbol: spi
Description: spitz
Alias: CG10334, CT29014, Dmel\CG10334, EP(2)2378, Spi, Spitz, anon-WO0118547.158, l(2)01068, l(2)37Fa, l(2)s3547, s-spi, sSpi, spitz, CG10334-PA, CG10334-PB, CG10334-PE, CG10334-PF, CG10334-PG, epidermal growth factor protein, spi-PA, spi-PB, spi-PE, spi-PF, spi-PG
Species: fruit fly
Products:     spi

Top Publications

  1. Corl A, Berger K, Ophir Shohat G, Gesch J, Simms J, Bartlett S, et al. Happyhour, a Ste20 family kinase, implicates EGFR signaling in ethanol-induced behaviors. Cell. 2009;137:949-60 pubmed publisher
    ..Inhibitors of the EGFR or components of its signaling pathway are thus potential pharmacotherapies for AUDs...
  2. Golembo M, Schweitzer R, Freeman M, Shilo B. Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop. Development. 1996;122:223-30 pubmed
    ..the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling...
  3. Mirkovic I, Mlodzik M. Cooperative activities of drosophila DE-cadherin and DN-cadherin regulate the cell motility process of ommatidial rotation. Development. 2006;133:3283-93 pubmed
    ..A similar input into mammalian E- and N-cadherins might function in the progression of diseases such as metastatic ovarian cancer. ..
  4. Urban S, Lee J, Freeman M. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell. 2001;107:173-82 pubmed
    ..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...
  5. Brown K, Freeman M. Egfr signalling defines a protective function for ommatidial orientation in the Drosophila eye. Development. 2003;130:5401-12 pubmed
  6. Schweitzer R, Shaharabany M, Seger R, Shilo B. Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev. 1995;9:1518-29 pubmed
    The spitz gene encoding a TGF-alpha homolog, has been shown to affect a subset of developmental processes that are similar to those regulated by DER, the Drosophila EGF receptor homolog...
  7. Guichard A, Roark M, Ronshaugen M, Bier E. brother of rhomboid, a rhomboid-related gene expressed during early Drosophila oogenesis, promotes EGF-R/MAPK signaling. Dev Biol. 2000;226:255-66 pubmed
    ..The Rhomboid protein has been proposed to promote presentation and/or processing of the membrane-bound Spitz (mSpi) EGF-related ligand to generate an active diffusible form of the ligand...
  8. Rutledge B, Zhang K, Bier E, Jan Y, Perrimon N. The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis. Genes Dev. 1992;6:1503-17 pubmed
    We describe the molecular characterization of the Drosophila gene spitz (spi), which encodes a putative 26-kD, EGF-like transmembrane protein that is structurally similar to TGF-alpha...
  9. Matsuoka S, Hiromi Y, Asaoka M. Egfr signaling controls the size of the stem cell precursor pool in the Drosophila ovary. Mech Dev. 2013;130:241-53 pubmed publisher
    ..While excess GSC formation is compensated by the adult stage, insufficient GSC formation can lead to adult ovarioles that completely lack GSCs, suggesting that ensuring an absolute size of the PGC pool is crucial for the GSC system...

More Information


  1. Huang Z, Shilo B, Kunes S. A retinal axon fascicle uses spitz, an EGF receptor ligand, to construct a synaptic cartridge in the brain of Drosophila. Cell. 1998;95:693-703 pubmed
    ..The EGFR ligand Spitz, a signal for ommatidial assembly in the compound eye, is transported to retinal axon termini in the brain where ..
  2. Lanoue B, Gordon M, Battye R, Jacobs J. Genetic analysis of vein function in the Drosophila embryonic nervous system. Genome. 2000;43:564-73 pubmed
    ..epidermal growth factor receptor (EGFR) may be activated by two ligands expressed in the embryonic nervous system, Spitz and Vein...
  3. Yang L, Baker N. Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. Dev Cell. 2003;4:359-69 pubmed
    ..Our results suggest that, rather than triggering all or none responses, EGFR coordinates partially independent processes as the eye differentiates. ..
  4. Salecker I, Clandinin T, Zipursky S. Hedgehog and Spitz: making a match between photoreceptor axons and their targets. Cell. 1998;95:587-90 pubmed
  5. Chen C, Kühnlein R, Eulenberg K, Vincent S, Affolter M, Schuh R. The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development. Development. 1998;125:4959-68 pubmed
    ..Furthermore, we provide evidence that the border between cells acquiring dorsal branch and dorsal trunk identity is established by the direct interaction of KNIRPS with a spalt cis-regulatory element. ..
  6. Duchek P, Rørth P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science. 2001;291:131-3 pubmed
    ..The transforming growth factor-alpha (TGF-alpha)-like ligand Gurken appears to serve as the guidance cue. To mediate this guidance function, EGFR signals via a pathway that is independent of Raf-MAP kinase and receptor-specific. ..
  7. Buchon N, Broderick N, Kuraishi T, Lemaitre B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol. 2010;8:152 pubmed publisher
    ..The EGFR pathway is activated by the EGF ligands, Spitz, Keren and Vein, the latter being induced in the surrounding visceral muscles in part under the control of the ..
  8. Tsruya R, Schlesinger A, Reich A, Gabay L, Sapir A, Shilo B. Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz. Genes Dev. 2002;16:222-34 pubmed publisher
    b>Spitz (Spi) is a TGFalpha homolog that is a cardinal ligand for the Drosophila EGF receptor throughout development. Cleavage of the ubiquitously expressed transmembrane form of Spi (mSpi) precedes EGF receptor activation...
  9. Gilboa L, Lehmann R. Soma-germline interactions coordinate homeostasis and growth in the Drosophila gonad. Nature. 2006;443:97-100 pubmed
    ..PGCs express the EGF receptor (EGFR) ligand Spitz, which is required for IC survival. In turn, ICs inhibit PGC proliferation...
  10. Wasserman J, Freeman M. An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell. 1998;95:355-64 pubmed
    ..cells this initial paracrine signaling event triggers an autocrine amplification by two other EGFR ligands, Spitz and Vein. Spitz only becomes an effective ligand in the presence of the multitransmembrane domain protein Rhomboid...
  11. Sepp K, Auld V. Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development. J Neurosci. 2003;23:8221-30 pubmed
    ..Mutant analysis also suggested that the EGFR ligands Spitz and Vein play roles in peripheral glial development...
  12. Kiger A, White Cooper H, Fuller M. Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature. 2000;407:750-4 pubmed
  13. Cordero J, Stefanatos R, Myant K, Vidal M, Sansom O. Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the Drosophila adult midgut. Development. 2012;139:4524-35 pubmed publisher
    ..we find that loss of Apc1 leads to the production of the interleukin-like ligands Upd2/3 and the EGF-like Spitz in a Myc-dependent manner...
  14. Yagi Y, Hayashi S. Role of the Drosophila EGF receptor in determination of the dorsoventral domains of escargot expression during primary neurogenesis. Genes Cells. 1997;2:41-53 pubmed
    ..These two kinds of regulation establish the early esg expression that prefigures the neuroectoderm patterning. ..
  15. Baker R, Young K, Feng L, Shi Y, Urban S. Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc Natl Acad Sci U S A. 2007;104:8257-62 pubmed
    ..were conducted with a substrate that we show is cleaved at two intramembrane sites within the previously defined Spitz substrate motif...
  16. Liu M, Lim T, Cai Y. The Drosophila female germline stem cell lineage acts to spatially restrict DPP function within the niche. Sci Signal. 2010;3:ra57 pubmed publisher
    ..Thus, our data reveal that the reciprocal crosstalk between the GSCs and the somatic cells defines the spatial limits of DPP action and therefore the extent of the GSC niche. ..
  17. Stemerdink C, Jacobs J. Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos. Development. 1997;124:3787-96 pubmed
    ..midline glia entering apoptosis at this stage can be increased by a loss or reduction of function in genes of the spitz group or Drosophila EGF receptor (DER) pathway...
  18. Brossier F, Jewett T, Sibley L, Urban S. A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc Natl Acad Sci U S A. 2005;102:4146-51 pubmed
    ..T. gondii rhomboids have clear homologues in other apicomplexans including malaria; thus, our findings provide a model for studying invasion by this deadly pathogen and offer a target for therapeutic intervention. ..
  19. Culi J, Martin Blanco E, Modolell J. The EGF receptor and N signalling pathways act antagonistically in Drosophila mesothorax bristle patterning. Development. 2001;128:299-308 pubmed
    ..Excess EGFR signalling can overrule lateral inhibition and allow adjacent cells to become SMCs and sensory organs. Thus, the EGFR and Notch pathways act antagonistically in notum macrochaetae determination. ..
  20. Lesokhin A, Yu S, Katz J, Baker N. Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila. Dev Biol. 1999;205:129-44 pubmed
    ..mutation is hypermorphic in vivo, but the DER function was elevated less than by ectopic expression of the ligand spitz. Ectopic spi promoted photoreceptor differentiation, even in the absence of R8 cells...
  21. Klämbt C, Jacobs J, Goodman C. The midline of the Drosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance. Cell. 1991;64:801-15 pubmed
    ..A genetic test of this model has utilized a number of mutations that, by either eliminating or altering the differentiation of various midline cells, perturb the development of the axon commissures in a predictable fashion. ..
  22. Schweitzer R, Howes R, Smith R, Shilo B, Freeman M. Inhibition of Drosophila EGF receptor activation by the secreted protein Argos. Nature. 1995;376:699-702 pubmed
    ..Its primary activating ligand is the Spitz protein, which is similar to mammalian TGF-alpha...
  23. Schnepp B, Grumbling G, Donaldson T, Simcox A. Vein is a novel component in the Drosophila epidermal growth factor receptor pathway with similarity to the neuregulins. Genes Dev. 1996;10:2302-13 pubmed
    ..Consequently, vn may promote tissue-specific receptor activation. Unlike two other ligands, Gurken (Grk) and Spitz (Spi), which are transforming growth factor alpha-like proteins, Vn has both an immunoglobulin-like and an EGF-..
  24. Schweitzer R, Shilo B. A thousand and one roles for the Drosophila EGF receptor. Trends Genet. 1997;13:191-6 pubmed
    ..The cellular mechanisms that translate EGFR activation to discrete cell fates are now the focus of intense studies. ..
  25. Jiang H, Edgar B. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development. 2009;136:483-93 pubmed publisher
    ..Two stronger EGFR ligands, Spitz and Keren, are expressed by the AMPs themselves and provide an additional, autocrine mitogenic stimulus to the ..
  26. Miller D, Cagan R. Local induction of patterning and programmed cell death in the developing Drosophila retina. Development. 1998;125:2327-35 pubmed
    ..Together, these signals refine the highly regular pattern observed in the adult retina. ..
  27. Baker N, Yu S. The EGF receptor defines domains of cell cycle progression and survival to regulate cell number in the developing Drosophila eye. Cell. 2001;104:699-708 pubmed
    ..Through proliferation and survival control, such signals couple the total number of uncommitted cells being generated to the neural patterning of the retina. ..
  28. Urban S, Schlieper D, Freeman M. Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids. Curr Biol. 2002;12:1507-12 pubmed
    ..Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early. ..
  29. Wappner P, Gabay L, Shilo B. Interactions between the EGF receptor and DPP pathways establish distinct cell fates in the tracheal placodes. Development. 1997;124:4707-16 pubmed
    ..We show that the EGF receptor pathway is activated by localized processing of the ligand SPITZ in the tracheal placodes and is responsible for the capacity to form the dorsal trunk and visceral branch...
  30. Zettl M, Adrain C, Strisovsky K, Lastun V, Freeman M. Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell. 2011;145:79-91 pubmed publisher
    ..Inactive cognates of enzymes are common, but their functions are mostly unclear; our data indicate that pseudoenzymes can readily evolve into regulatory proteins, suggesting that this may be a significant evolutionary mechanism. ..
  31. Wasserman J, Urban S, Freeman M. A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling. Genes Dev. 2000;14:1651-63 pubmed
    ..mechanism of Rhomboid function but genetic evidence suggests that it controls the activation of the ligand Spitz, a TGFalpha-like factor...
  32. Tio M, Ma C, Moses K. spitz, a Drosophila homolog of transforming growth factor-alpha, is required in the founding photoreceptor cells of the compound eye facets. Mech Dev. 1994;48:13-23 pubmed
    ..We report that recessive spitz loss-of-function mutations affect compound eye development...
  33. Yogev S, Schejter E, Shilo B. Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases. EMBO J. 2008;27:1219-30 pubmed publisher
    ..Rho-2 and Rho-3, which are expressed in the germ line and in the developing eye, respectively, cleave the Spitz precursor and Star already in the ER, in addition to their activity in the late compartment...
  34. Kerber B, Fellert S, Hoch M. Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell proliferation in the insect kidney. Genes Dev. 1998;12:1781-6 pubmed
    ..Seven-up in turn is capable of regulating the transcription of cell cycle regulators. ..
  35. Urban S, Brown G, Freeman M. EGF receptor signalling protects smooth-cuticle cells from apoptosis during Drosophila ventral epidermis development. Development. 2004;131:1835-45 pubmed
    ..and EGFR signalling determines the segmentally repeated pattern of alternating denticle belts and smooth cuticle: spitz group genes, which encode factors that stimulate EGFR signalling, induce the denticle fate, while Wingless ..
  36. McDonald J, Pinheiro E, Kadlec L, Schupbach T, Montell D. Multiple EGFR ligands participate in guiding migrating border cells. Dev Biol. 2006;296:94-103 pubmed
    ..Two ligands, Keren and Spitz, guided border cells whereas the other ligands, Gurken and Vein, did not...
  37. Jekely G, Sung H, Luque C, Rørth P. Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Dev Cell. 2005;9:197-207 pubmed
    ..Cbl and Sprint both regulate early steps of RTK endocytosis. Thus, a physiological role of RTK endocytosis is to ensure localized intracellular response to guidance cues by stimulating spatial restriction of signaling. ..
  38. Dequier E, Souid S, Pal M, Maroy P, Lepesant J, Yanicostas C. Top-DER- and Dpp-dependent requirements for the Drosophila fos/kayak gene in follicular epithelium morphogenesis. Mech Dev. 2001;106:47-60 pubmed
    ..This suggests that in somatic follicle cells, Dfos controls the expression of one or several factors that are necessary for these processes in underlying germinal nurse cells. ..
  39. Grigorian M, Mandal L, Hakimi M, Ortiz I, Hartenstein V. The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm. Dev Biol. 2011;353:105-18 pubmed publisher
  40. Lee J, Urban S, Garvey C, Freeman M. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell. 2001;107:161-71 pubmed
    ..that they control receptor signaling by regulating intracellular trafficking and proteolysis of the ligand Spitz. Star is present throughout the secretory pathway and is required to export Spitz from the endoplasmic reticulum ..
  41. Mayer U, Nusslein Volhard C. A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev. 1988;2:1496-511 pubmed
    Mutations in the genes spitz (spi), Star (S), single-minded (sim), pointed (pnt), rhomboid (rho) (all zygotic), and sichel (sic) (maternal), collectively called the spitz group, cause similar pattern alterations in ventral ectodermal ..
  42. Szuts D, Eresh S, Bienz M. Functional intertwining of Dpp and EGFR signaling during Drosophila endoderm induction. Genes Dev. 1998;12:2022-35 pubmed
    ..We discuss the potential significance of why an inductive process might use a secondary signal whose function is intertwined with that of the primary signal. ..
  43. Sudarsan V, Pasalodos Sanchez S, Wan S, Gampel A, Skaer H. A genetic hierarchy establishes mitogenic signalling and mitotic competence in the renal tubules of Drosophila. Development. 2002;129:935-44 pubmed
    ..of tubule cells, the tip cells, which express the protease Rhomboid and are thus able to secrete the EGF ligand, Spitz. We show that the response to EGF signalling, and in consequence cell division, is patterned by the specification ..
  44. Dominguez M, Wasserman J, Freeman M. Multiple functions of the EGF receptor in Drosophila eye development. Curr Biol. 1998;8:1039-48 pubmed
    ..At least five distinct functions of EGFR signalling need to be integrated during fly eye development. These include roles in cell proliferation, survival and differentiation. ..
  45. Freeman M. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor. Mech Dev. 1994;48:25-33 pubmed
    ..that modify the phenotype caused by ectopic expression of the rhomboid gene in the eye, I have discovered that the spitz gene is required for photoreceptor determination...
  46. Estes P, Fulkerson E, Zhang Y. Identification of motifs that are conserved in 12 Drosophila species and regulate midline glia vs. neuron expression. Genetics. 2008;178:787-99 pubmed publisher
    ..These results suggest short, highly conserved genomic sequences flanking Drosophila midline genes are indicative of functional regulatory regions and that small changes within these sequences can alter the expression pattern of a gene. ..
  47. Freeman M. Feedback control of intercellular signalling in development. Nature. 2000;408:313-9 pubmed
    ..These feedback interactions can impart precision, robustness and versatility to intercellular signals. Feedback failure can cause disease. ..
  48. Tio M, Moses K. The Drosophila TGF alpha homolog Spitz acts in photoreceptor recruitment in the developing retina. Development. 1997;124:343-51 pubmed
    ..is bound by several activating ligands including Transforming Growth Factor-alpha in vertebrates, and its homolog Spitz in Drosophila...
  49. Guichard A, Biehs B, Sturtevant M, Wickline L, Chacko J, Howard K, et al. rhomboid and Star interact synergistically to promote EGFR/MAPK signaling during Drosophila wing vein development. Development. 1999;126:2663-76 pubmed
    ..Among these genes, Egfr encodes the Drosophila EGF-Receptor, spitz (spi) and vein (vn) encode EGF-related ligands, and rhomboid (rho) and Star (S) encode membrane proteins...
  50. Ninov N, Manjón C, Martin Blanco E. Dynamic control of cell cycle and growth coupling by ecdysone, EGFR, and PI3K signaling in Drosophila histoblasts. PLoS Biol. 2009;7:e1000079 pubmed publisher
    ..It sets the stage for the comprehensive understanding of the coordination of cell growth and cell-cycle progression in complex multicellular eukaryotes. ..
  51. Reeves G, Kalifa R, Klein D, Lemmon M, Shvartsman S. Computational analysis of EGFR inhibition by Argos. Dev Biol. 2005;284:523-35 pubmed
    ..receptor, and the only known secreted receptor tyrosine kinase inhibitor, acts by sequestering the EGFR ligand Spitz. We use computational modeling to show that this biochemically-determined mechanism of Argos action can explain ..
  52. Buff E, Carmena A, Gisselbrecht S, Jimenez F, Michelson A. Signalling by the Drosophila epidermal growth factor receptor is required for the specification and diversification of embryonic muscle progenitors. Development. 1998;125:2075-86 pubmed
    ..In the absence of the receptor or its ligand, SPITZ, specific progenitors fail to segregate. The resulting unspecified mesodermal cells undergo programmed cell death...
  53. Nishimura M, Inoue Y, Hayashi S. A wave of EGFR signaling determines cell alignment and intercalation in the Drosophila tracheal placode. Development. 2007;134:4273-82 pubmed
  54. Kurada P, White K. Ras promotes cell survival in Drosophila by downregulating hid expression. Cell. 1998;95:319-29 pubmed
    ..Null alleles of hid recapitulate the antiapoptotic activities of Ras/MAPK, providing genetic evidence that downregulation of hid is an important mechanism by which Ras promotes survival. ..
  55. Parrott B, Hudson A, Brady R, Schulz C. Control of germline stem cell division frequency--a novel, developmentally regulated role for epidermal growth factor signaling. PLoS ONE. 2012;7:e36460 pubmed publisher
    ..In addition, regulation of GSC division frequency is a specific role for EGF signaling as it is not affected in all tumor models. These data advance our understanding concerning stem cell dynamics in normal tissues and in a tumor model. ..
  56. Hasson P, Egoz N, Winkler C, Volohonsky G, Jia S, Dinur T, et al. EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output. Nat Genet. 2005;37:101-5 pubmed
    ..Thus, Gro is a new junction between signaling pathways, enabling EGFR signaling to antagonize transcriptional output by Notch and potentially other Gro-dependent pathways. ..
  57. Brown K, Baonza A, Freeman M. Epithelial cell adhesion in the developing Drosophila retina is regulated by Atonal and the EGF receptor pathway. Dev Biol. 2006;300:710-21 pubmed
    ..These observations define a new function for EGFR signalling in eye development and illustrate a mechanism for the control of epithelial morphology by developmental signals. ..
  58. Sarkar A, Parikh N, Hearn S, Fuller M, Tazuke S, Schulz C. Antagonistic roles of Rac and Rho in organizing the germ cell microenvironment. Curr Biol. 2007;17:1253-8 pubmed
    ..We show that germ cells signal via the Egf class ligand Spitz (Spi) and provide evidence that the Egfr associates with and acts through the guanine nucleotide exchange factor ..
  59. Hsiung F, Griffis E, Pickup A, Powers M, Moses K. Function of the Drosophila TGF-alpha homolog Spitz is controlled by Star and interacts directly with Star. Mech Dev. 2001;107:13-23 pubmed
    Drosophila Spitz is a homolog of transforming growth factor alpha (TGF-alpha) and is an activating ligand for the EGF receptor (Egfr). It has been shown that Star is required for Spitz activity...
  60. Crews S. Control of cell lineage-specific development and transcription by bHLH-PAS proteins. Genes Dev. 1998;12:607-20 pubmed
  61. Gallio M, Englund C, Kylsten P, Samakovlis C. Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline. Development. 2004;131:3605-14 pubmed
    ..We propose that Egfr activation provides a necessary switch for the interpretation of a yet unknown repellent function of the midline. ..
  62. Kubota K, Goto S, Eto K, Hayashi S. EGF receptor attenuates Dpp signaling and helps to distinguish the wing and leg cell fates in Drosophila. Development. 2000;127:3769-76 pubmed
    ..Differential activation of the two signals and the cross talk between them critically affect this cell fate choice. ..
  63. Gabay L, Seger R, Shilo B. In situ activation pattern of Drosophila EGF receptor pathway during development. Science. 1997;277:1103-6 pubmed
    ..This in situ approach can be used to monitor other receptor-triggered pathways in a wide range of organisms. ..
  64. Dumstrei K, Nassif C, Abboud G, Aryai A, Hartenstein V. EGFR signaling is required for the differentiation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head. Development. 1998;125:3417-26 pubmed
    ..Localized activation of the TGFalpha homolog Spitz (Spi) in the mesectoderm is achieved by the products of the genes rhomboid and Star...
  65. Yasugi T, Sugie A, Umetsu D, Tabata T. Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe. Development. 2010;137:3193-203 pubmed publisher
    ..is regulated by transient expression of Rhomboid (Rho), which is required for the maturation of the EGF ligand Spitz. Rho expression is also regulated by the EGFR signal...
  66. Gabay L, Scholz H, Golembo M, Klaes A, Shilo B, Klämbt C. EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm. Development. 1996;122:3355-62 pubmed
    ..The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates. ..
  67. Golembo M, Raz E, Shilo B. The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. Development. 1996;122:3363-70 pubmed
    The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm...
  68. Gallio M, Sturgill G, Rather P, Kylsten P. A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes. Proc Natl Acad Sci U S A. 2002;99:12208-13 pubmed
    ..This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated...
  69. Lemberg M, Menendez J, Misik A, Garcia M, Koth C, Freeman M. Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases. EMBO J. 2005;24:464-72 pubmed
    ..We identify a motif shared between rhomboids and the recently discovered derlins, which participate in translocation of misfolded membrane proteins. ..
  70. Yogev S, Schejter E, Shilo B. Polarized secretion of Drosophila EGFR ligand from photoreceptor neurons is controlled by ER localization of the ligand-processing machinery. PLoS Biol. 2010;8: pubmed publisher
    ..the developing Drosophila visual system, photoreceptor neurons secrete the epidermal growth factor receptor ligand Spitz (Spi) from their cell bodies, as well as from their axonal termini...
  71. Rousso T, Lynch J, Yogev S, Roth S, Schejter E, Shilo B. Generation of distinct signaling modes via diversification of the Egfr ligand-processing cassette. Development. 2010;137:3427-37 pubmed publisher
    ..Diversification of the Egfr signaling pathway appears to have coupled gene duplication events with modulation of the biochemical properties and subcellular localization patterns of Rhomboid proteases and their substrates...
  72. Freeman M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell. 1996;87:651-60 pubmed
    ..These results broaden our view of eye development to include the whole ommatidium and suggest that reiterative activation of DER is critical for triggering the differentiation of all cell types. ..
  73. Urban S, Freeman M. Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol Cell. 2003;11:1425-34 pubmed
    ..how specificity is achieved: Drosophila Rhomboid-1 is a site-specific protease that recognizes its substrate Spitz by a small region of the Spitz transmembrane domain (TMD)...
  74. Ren F, Wang B, Yue T, Yun E, Ip Y, Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A. 2010;107:21064-9 pubmed publisher
    ..Finally, we show that the Hpo pathway mediator Yorkie (Yki) is also required in precursor cells for injury-induced ISC proliferation in response to tissue-damaging reagent DSS. ..
  75. Bier E, Jan L, Jan Y. rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev. 1990;4:190-203 pubmed
    ..We hypothesize that rho acts very early in differentiation pathways to specify the identities of domains and isolated precursor cells. Sequence analysis suggests that this transcript codes for a trans-membrane protein. ..