Genomes and Genes
Gene Symbol: E(spl)m8-HLH
Description: Enhancer of split m8, helix-loop-helix
Alias: CG8365, Dmel\CG8365, E(Spl), E(spl), E(spl) m8, E(spl)-C, E(spl)-m8, E(spl)M8, E(spl)bHLH, E(spl)m8, En(spl), En(spl)-C, Espl, HLHm8, Hes, Su(H)[[m8]], anon-EST:Liang-1.71, bHLHb36, clone 1.71, e(spl), l(3)96Fd, enhancer of split m8, helix-loop-helix, CG8365-PA, E(spl)m8, E(spl)m8-HLH-PA, Enhancer-of-split, enhancer of split, enhancer of split m8, enhancer-of-split-m8
Species: fruit fly
- Giebel B, Campos Ortega J. Functional dissection of the Drosophila enhancer of split protein, a suppressor of neurogenesis. Proc Natl Acad Sci U S A. 1997;94:6250-4 pubmedThe Enhancer of split [E(spl)] gene complex of Drosophila comprises seven related genes encoding a special type of basic helix-loop-helix proteins, the function of which is to suppress the neural developmental fate...
- Nagel A, Maier D, Krauss S, Mezger M, Preiss A. Neurogenic phenotypes induced by RNA interference with bHLH genes of the Enhancer of split complex of Drosophila melanogaster. Genesis. 2004;39:105-14 pubmedThe Enhancer of split gene complex [E(spl)-C] of Drosophila melanogaster harbors seven highly related genes encoding transcriptional regulators with a basic helix-loop-helix (bHLH) domain...
- Artavanis Tsakonas S, Matsuno K, Fortini M. Notch signaling. Science. 1995;268:225-32 pubmed..Several vertebrate Notch receptors have also been discovered recently and play important roles in normal development and tumorigenesis. ..
- Klein T, Seugnet L, Haenlin M, Martinez Arias A. Two different activities of Suppressor of Hairless during wing development in Drosophila. Development. 2000;127:3553-66 pubmed..After its release Su(H) can activate gene expression in absence of Nintra. ..
- Knust E, Bremer K, Vässin H, Ziemer A, Tepass U, Campos Ortega J. The enhancer of split locus and neurogenesis in Drosophila melanogaster. Dev Biol. 1987;122:262-73 pubmedb>Enhancer of split (E(spl)) is one of a group of so-called neurogenic genes of Drosophila...
- Powell P, Wesley C, Spencer S, Cagan R. Scabrous complexes with Notch to mediate boundary formation. Nature. 2001;409:626-30 pubmed..The result is a regulation of Notch activity that sharpens proneural cluster boundaries and ensures establishment of single pioneer neurons. ..
- Singson A, Leviten M, Bang A, Hua X, Posakony J. Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling. Genes Dev. 1994;8:2058-71 pubmed..Interestingly, these ac-sc target genes, including Bearded, Enhancer of split m7, Enhancer of split m8, and scabrous, are all known or believed to function in the selection of a single SOP from each PNC, a ..
- Artavanis Tsakonas S, Simpson P. Choosing a cell fate: a view from the Notch locus. Trends Genet. 1991;7:403-8 pubmed..The Notch locus appears to play a central and general role in the regulative events that control the local architecture of the final cellular pattern in several tissues, among them being the central and peripheral nervous systems. ..
- Kramatschek B, Campos Ortega J. Neuroectodermal transcription of the Drosophila neurogenic genes E(spl) and HLH-m5 is regulated by proneural genes. Development. 1994;120:815-26 pubmedThe Enhancer of split gene complex (E(SPL)-C) of Drosophila comprises seven genes encoding bHLH proteins, which are required by neuroectodermal cells for epidermal development...
- Maeder M, Polansky B, Robson B, EASTMAN D. Phylogenetic footprinting analysis in the upstream regulatory regions of the Drosophila enhancer of split genes. Genetics. 2007;177:1377-94 pubmed..development Suppressor of Hairless [Su(H)]-dependent Notch activation upregulates transcription of the Enhancer of split-Complex [E(spl)-C] genes...
- Baker N, Yu S. Proneural function of neurogenic genes in the developing Drosophila eye. Curr Biol. 1997;7:122-32 pubmed..Secondly, consecutive regulatory processes become temporally coupled, so that these events follow on from each other, without gaps or overlaps. ..
- Lecourtois M, Schweisguth F. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling. Genes Dev. 1995;9:2598-608 pubmed..in these Su(H) mutant embryos was associated with a failure to express the m5 and m8 genes from the Enhancer of split Complex [E(spl)-C]...
- Campos Ortega J. The genetics of the Drosophila achaete-scute gene complex: a historical appraisal. Int J Dev Biol. 1998;42:291-7 pubmed..Due to their intricate organization, these genes have occupied geneticists and developmental biologists for many years. Here, genetic studies on the complex are discussed from a historical point of view. ..
- Fisher A, Caudy M. Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates. Genes Dev. 1998;12:1931-40 pubmed
- Wech I, Bray S, Delidakis C, Preiss A. Distinct expression patterns of different enhancer of split bHLH genes during embryogenesis of Drosophila melanogaster. Dev Genes Evol. 1999;209:370-5 pubmed
- Fisher A, Caudy M. The function of hairy-related bHLH repressor proteins in cell fate decisions. Bioessays. 1998;20:298-306 pubmed..This general function in cell fate specification has been conserved from Drosophila to vertebrates and has implications for human disease pathogenesis. ..
- Kahali B, Bose A, Karandikar U, Bishop C, Bidwai A. On the mechanism underlying the divergent retinal and bristle defects of M8* (E(spl)D) in Drosophila. Genesis. 2009;47:456-68 pubmed publisher..Multisite phosphorylation could serve as a checkpoint to enable a precise onset of repression, and this is bypassed in M8*. Additional implications are discussed. ..
- Kahali B, Kim J, Karandikar U, Bishop C, Bidwai A. Evidence that the C-terminal domain (CtD) autoinhibits neural repression by Drosophila E(spl)M8. Genesis. 2010;48:44-55 pubmed publisher..These studies provide evidence that autoinhibition by the CtD regulates M8 activity in a phosphorylation-dependent manner. ..
- Lee T, Ding T, Chen Z, Rajendran V, Scherr H, Lackey M, et al. The E1 ubiquitin-activating enzyme Uba1 in Drosophila controls apoptosis autonomously and tissue growth non-autonomously. Development. 2008;135:43-52 pubmed..In summary, the phenotypic analysis of Uba1 demonstrates that impaired ubiquitin conjugation has significant consequences for the organism, and may implicate Uba1 as a tumor suppressor gene. ..
- Knust E, Tietze K, Campos Ortega J. Molecular analysis of the neurogenic locus Enhancer of split of Drosophila melanogaster. EMBO J. 1987;6:4113-23 pubmedb>Enhancer of split [E(spl)], one of the neurogenic loci of Drosophila, is located in bands 96F8-13. One hundred and fifty kilobases of genomic DNA, spanning the E(spl) locus, were cloned by chromosomal walking...
- Campuzano S, Modolell J. Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 1992;8:202-8 pubmed..Neuroblasts or sensory organ mother cells are born within these clusters. Thus, the patterns of expression of the AS-C genes help to define the topology of the nervous system. ..
- Baker N, Yu S, Han D. Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye. Curr Biol. 1996;6:1290-301 pubmed..Serrate, and by monitoring expression of the atonal-dependant gene scabrous and of the Notch-dependent Enhancer of split genes...
- Skeath J, Carroll S. Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. Development. 1992;114:939-46 pubmed..It appears that one key function of the neurogenic genes is to silence proneural gene expression within the nonsegregating cells of the initial ectodermal clusters, thereby permitting epidermal development. ..
- Bailey A, Posakony J. Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes Dev. 1995;9:2609-22 pubmed..receptor protein, Suppressor of Hairless [Su(H)], which encodes a DNA-binding transcription factor, and the Enhancer of split gene complex [E(spl)-C], which includes seven transcription units that encode basic helix-loop-helix (bHLH) ..
- Jennings B, Preiss A, Delidakis C, Bray S. The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo. Development. 1994;120:3537-48 pubmedThe Enhancer of split locus is required during many cell-fate decisions in Drosophila, including the segregation of neural precursors in the embryo...
- Nolo R, Abbott L, Bellen H. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell. 2000;102:349-62 pubmed..Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs. ..
- Culi J, Modolell J. Proneural gene self-stimulation in neural precursors: an essential mechanism for sense organ development that is regulated by Notch signaling. Genes Dev. 1998;12:2036-47 pubmed..Cells neighboring the SMC do not acquire the neural fate because the Notch signaling pathway effectors, the Enhancer of split bHLH proteins, block this proneural gene self-stimulatory loop, possibly by antagonizing the action on the ..
- Maier D, Marte B, Schafer W, Yu Y, Preiss A. Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proc Natl Acad Sci U S A. 1993;90:5464-8 pubmedThe Enhancer of split [E(spl)] gene complex belongs to the class of neurogenic loci, which, in a concerted action, govern neurogenesis in Drosophila...
- Giagtzoglou N, Koumbanakis K, Fullard J, Zarifi I, Delidakis C. Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment. J Biol Chem. 2005;280:1299-305 pubmed..Most prominent among the factors antagonizing proneural protein activity are the HES basic helix-loop-helix proteins...
- Paroush Z, Finley R, Kidd T, Wainwright S, Ingham P, Brent R, et al. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell. 1994;79:805-15 pubmed..gro) protein binds specifically to hairy and also to hairy-related bHLH proteins encoded by deadpan and the Enhancer of split complex. The C-terminal WRPW motif present in all these bHLH proteins is essential for this interaction...
- Oellers N, Dehio M, Knust E. bHLH proteins encoded by the Enhancer of split complex of Drosophila negatively interfere with transcriptional activation mediated by proneural genes. Mol Gen Genet. 1994;244:465-73 pubmedThe Enhancer of split complex [E(SPL)-C] of Drosophila participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo...
- Wurmbach E, Wech I, Preiss A. The Enhancer of split complex of Drosophila melanogaster harbors three classes of Notch responsive genes. Mech Dev. 1999;80:171-80 pubmed..In Drosophila, the majority of Notch target genes known so far is located in the Enhancer of split complex (E(spl)-C), encoding small basic helix-loop-helix (bHLH) proteins that presumably act as ..
- Lieber T, Kidd S, Alcamo E, Corbin V, Young M. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev. 1993;7:1949-65 pubmed..Genes of the Enhancer of split complex act after Notch...
- Cave J, Loh F, Surpris J, Xia L, Caudy M. A DNA transcription code for cell-specific gene activation by notch signaling. Curr Biol. 2005;15:94-104 pubmed..Thus, SPS+A is an architectural DNA transcription code that programs a cell-specific pattern of gene expression. ..
- Tata F, Hartley D. Inhibition of cell fate in Drosophila by Enhancer of split genes. Mech Dev. 1995;51:305-15 pubmed..Amongst the genes at the neurogenic locus, Enhancer of split is a family of seven related genes that encode proteins containing the basic helix-loop-helix motif ..
- Giagtzoglou N, Alifragis P, Koumbanakis K, Delidakis C. Two modes of recruitment of E(spl) repressors onto target genes. Development. 2003;130:259-70 pubmed..Irrespective of whether E(spl) are recruited via direct DNA binding or interaction with proneural proteins, the co-repressor Groucho is always needed for target gene repression. ..
- Greenwald I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 1998;12:1751-62 pubmed
- San Juán B, Baonza A. The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev Biol. 2011;352:70-82 pubmed publisher..We show that in addition to dpn, Notch signaling must be regulating other genes during this process that act redundantly with dpn. ..
- Karandikar U, Trott R, Yin J, Bishop C, Bidwai A. Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8. Mech Dev. 2004;121:273-86 pubmed..Our studies uncover a novel functional domain that is conserved amongst a subset of E(spl)/Hes repressors in Drosophila and mammals, and suggests a potential role for CK2 during retinal patterning.
- Cooper M, Bray S. R7 photoreceptor specification requires Notch activity. Curr Biol. 2000;10:1507-10 pubmed
- Herz H, Woodfield S, Chen Z, Bolduc C, Bergmann A. Common and distinct genetic properties of ESCRT-II components in Drosophila. PLoS ONE. 2009;4:e4165 pubmed publisher..Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation. ..
- Lai E. Notch signaling: control of cell communication and cell fate. Development. 2004;131:965-73 pubmed..This primer describes the mechanism of Notch signal transduction and how it is used to control the formation of biological patterns. ..
- Alifragis P, Poortinga G, Parkhurst S, Delidakis C. A network of interacting transcriptional regulators involved in Drosophila neural fate specification revealed by the yeast two-hybrid system. Proc Natl Acad Sci U S A. 1997;94:13099-104 pubmed..of the proneural genes, such as those of the achaete-scute complex, and antagonized by the products of the Enhancer of split [E(spl)] complex, hairy, and extramacrochaetae...
- Trott R, Kalive M, Paroush Z, Bidwai A. Drosophila melanogaster casein kinase II interacts with and phosphorylates the basic helix-loop-helix proteins m5, m7, and m8 derived from the Enhancer of split complex. J Biol Chem. 2001;276:2159-67 pubmed..isolated in this screen encodes m7, a basic helix-loop-helix (bHLH)-type transcription factor encoded by the Enhancer of split complex (E(spl)C), which regulates neurogenesis...
- Castro B, Barolo S, Bailey A, Posakony J. Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless. Development. 2005;132:3333-44 pubmed publisher..Our work elucidates the regulatory logic by which N signaling and the proneural proteins cooperate to create the neural precursor/epidermal cell fate distinction during lateral inhibition...
- Hinz U, Giebel B, Campos Ortega J. The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. Cell. 1994;76:77-87 pubmed..Finally, the bHLH domain is necessary and sufficient to mediate the proneural function, to activate neurogenic genes, and to allow lateral inhibition. ..
- Wesley C. Notch and wingless regulate expression of cuticle patterning genes. Mol Cell Biol. 1999;19:5743-58 pubmed
- San Juán B, Andrade Zapata I, Baonza A. The bHLH factors Dpn and members of the E(spl) complex mediate the function of Notch signalling regulating cell proliferation during wing disc development. Biol Open. 2012;1:667-76 pubmed publisher..Here, we show that the Hes vertebrate homolog, deadpan (dpn), and the Enhancer-of-split complex (E(spl)C) genes act redundantly and ..
- Schrons H, Knust E, Campos Ortega J. The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. Genetics. 1992;132:481-503 pubmedThe Enhancer of split complex [E(spl)-C] of Drosophila melanogaster is located in the 96F region of the third chromosome and comprises at least seven structurally related genes, HLH-m delta, HLH-m gamma, HLH-m beta, HLH-m3, HLH-m5, HLH-..
- Dawson S, Turner D, Weintraub H, Parkhurst S. Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression. Mol Cell Biol. 1995;15:6923-31 pubmedThe Hairy/Enhancer of split/Deadpan family of basic helix-loop-helix (bHLH) proteins function as transcriptional repressors...
- Zacharioudaki E, Magadi S, Delidakis C. bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development. 2012;139:1258-69 pubmed publisher..Therefore, E(spl) and Dpn act together to maintain the NB in a self-renewing state, a process in which they are assisted by Notch, which sustains expression of the E(spl) subset. ..
- Mumm J, Kopan R. Notch signaling: from the outside in. Dev Biol. 2000;228:151-65 pubmed
- Matsuno K, Diederich R, Go M, Blaumueller C, Artavanis Tsakonas S. Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats. Development. 1995;121:2633-44 pubmed..On the basis of these findings, we propose a model wherein Deltex regulates Notch activity by antagonizing the interaction between Notch and Suppressor of Hairless. ..
- Herz H, Chen Z, Scherr H, Lackey M, Bolduc C, Bergmann A. vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis. Development. 2006;133:1871-80 pubmed..In summary, the phenotypic analysis of vps25 mutants highlights the importance of receptor downregulation by endosomal protein sorting for appropriate tissue homeostasis, and may serve as a model for human cancer. ..
- Jennings B, Tyler D, Bray S. Target specificities of Drosophila enhancer of split basic helix-loop-helix proteins. Mol Cell Biol. 1999;19:4600-10 pubmedSeven Enhancer of split genes in Drosophila melanogaster encode basic-helix-loop-helix transcription factors which are components of the Notch signalling pathway...
- Lai E, Bodner R, Posakony J. The enhancer of split complex of Drosophila includes four Notch-regulated members of the bearded gene family. Development. 2000;127:3441-55 pubmedDuring Drosophila development, transcriptional activation of genes of the Enhancer of split Complex (E(spl)-C) is a major response to cell-cell signaling via the Notch (N) receptor...
- Hartley D, Preiss A, Artavanis Tsakonas S. A deduced gene product from the Drosophila neurogenic locus, enhancer of split, shows homology to mammalian G-protein beta subunit. Cell. 1988;55:785-95 pubmed..One of the neurogenic genes, Enhancer of split, is particularly noteworthy in its genetic interactions with Notch and Delta, which both appear to code for ..
- Lai E. Drosophila tufted is a gain-of-function allele of the proneural gene amos. Genetics. 2003;163:1413-25 pubmed..This phenomenon seems instead to be related to their shared ability to activate Asense and Senseless. ..
- Bhattacharya A, Baker N. The HLH protein Extramacrochaetae is required for R7 cell and cone cell fates in the Drosophila eye. Dev Biol. 2009;327:288-300 pubmed publisher..A model is proposed in which Extramacrochaetae acts in parallel to or as a feed-forward regulator of the E(spl)-Complex to promote Notch signaling in particular cellular contexts. ..
- Preiss A, Hartley D, Artavanis Tsakonas S. The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila. EMBO J. 1988;7:3917-27 pubmed..We describe here a molecular analysis of Enhancer of split [E(spl)], a third neurogenic locus, which displays striking genetic interactions with both Notch and Delta, ..
- Lai E, Tam B, Rubin G. Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs. Genes Dev. 2005;19:1067-80 pubmed..Collectively, these data establish insights into miRNA target recognition and demonstrate that the Notch signaling pathway is a major target of miRNA-mediated regulation in Drosophila. ..
- Krejci A, Bray S. Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers. Genes Dev. 2007;21:1322-7 pubmed..Unexpectedly, Su(H) occupancy was significantly and transiently increased following Notch activation, suggesting a more dynamic interaction with targets than hitherto proposed. ..
- Delidakis C, Preiss A, Hartley D, Artavanis Tsakonas S. Two genetically and molecularly distinct functions involved in early neurogenesis reside within the Enhancer of split locus of Drosophila melanogaster. Genetics. 1991;129:803-23 pubmedMolecular correlation of the genetic aspects of the function of the neurogenic gene Enhancer of split [E(spl)] has previously been hampered by the densely transcribed nature of the chromosomal region within which it resides...
- Ligoxygakis P, Bray S, Apidianakis Y, Delidakis C. Ectopic expression of individual E(spl) genes has differential effects on different cell fate decisions and underscores the biphasic requirement for notch activity in wing margin establishment in Drosophila. Development. 1999;126:2205-14 pubmedA common consequence of Notch signalling in Drosophila is the transcriptional activation of seven Enhancer of split [E(spl)] genes, which encode a family of closely related basic-helix-loop-helix transcriptional repressors...
- Jafar Nejad H, Acar M, Nolo R, Lacin H, Pan H, Parkhurst S, et al. Senseless acts as a binary switch during sensory organ precursor selection. Genes Dev. 2003;17:2966-78 pubmed..In the presumptive SOPs that express high levels of Sens, it acts as a transcriptional activator and synergizes with proneural proteins. We therefore propose that Sens acts as a binary switch that is fundamental to SOP selection...
- Nakao K, Campos Ortega J. Persistent expression of genes of the enhancer of split complex suppresses neural development in Drosophila. Neuron. 1996;16:275-86 pubmed..These findings indicate that proneural and E(spl) proteins exert antagonistic functions. ..
- Nagel A, Yu Y, Preiss A. Enhancer of split [E(spl)(D)] is a gro-independent, hypermorphic mutation in Drosophila. Dev Genet. 1999;25:168-79 pubmedb>Enhancer of split [E(spl)] refers to a gene complex in Drosophila melanogaster, which contains a number of target genes of the Notch signaling pathway...
- Simpson P. Notch and the choice of cell fate in Drosophila neuroepithelium. Trends Genet. 1990;6:343-5 pubmed
- Delidakis C, Artavanis Tsakonas S. The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins. Proc Natl Acad Sci U S A. 1992;89:8731-5 pubmed..We report the structure of four additional HLH-encoding genes that reside in the E(spl) complex and provide evidence that we have now identified all the remaining members of the E(spl) HLH cluster. ..
- de Celis J, Garcia Bellido A, Bray S. Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. Development. 1996;122:359-69 pubmed..We find that Notch is locally activated in these cells, as demonstrated by the restricted expression of the Enhancer of split proteins in dorsal and ventral cells abutting the D/V boundary throughout the third larval instar...