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General Information
Symbol
Dmel\E(spl)m8-HLH
Species
D. melanogaster
Name
Enhancer of split m8, helix-loop-helix
Annotation Symbol
CG8365
Feature Type
FlyBase ID
FBgn0000591
Gene Model Status
Stock Availability
Gene Snapshot
In progress.Contributions welcome.
Also Known As
m8, E(spl)m8, E(spl), Enhancer of split, E(spl)-m8
Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:26,040,240..26,041,008 [+]
Recombination map
3-89
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
Summaries
Gene Group (FlyBase)
ENHANCER OF SPLIT GENE COMPLEX -
The Enhancer of split complex (E(spl)-C) of D.mel is a well characterized genetic locus on chromosome 3R containing 12 genes - with the exception of Kaz-m1, all are Notch responsive. Seven genes are basic helix-loop-helix (bHLH) transcription factors, four are bearded family genes. Kaz-m1 is unrelated, sharing some sequence similarity to Kazal class protease inhibitors. (Adapted from FBrf0211195).
BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS -
Basic helix-loop-helix (bHLH) transcription factors are sequence-specific DNA-binding proteins that regulate transcription. They are characterized by a 60 amino acid region comprising a basic DNA binding domain followed by a HLH motif formed from two amphipathic α-helices connected by a loop. bHLH transcription factors form homo- and hetero-dimeric complexes, which bind to a E box consensus sequence. (Adapted from PMID:15186484).
Protein Function (UniProtKB)
Participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo (PubMed:2540957). Transcriptional repressor (PubMed:8001118). Binds DNA on N-box motifs: 5'-CACNAG-3' (PubMed:8001118). Part of the Notch signaling pathway (PubMed:22357926).
(UniProt, P13098)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
E(spl): Enhancer of split
Locus involved in the differentiation of the neural ectoderm into neuroblasts and epidermoblasts. Increased levels of gene product favor epidermal differentiation, whereas decreased levels favor neuronal differentiation. Locus originally identified by the split-enhancing feature of a dominant gain-of-function mutation. Loss of function mutations are lethals and are described separately. A weak hypomorphic allele described as gro (groucho) is also described below. E(spl) causes spl/+ to display a split phenotype and elicits a more extreme phenotype in spl/spl and spl/Y. The spl-enhancing effect of E(spl)1 is suppressed in flies heterozygous for Dl (Shepard, Boverman, and Muskavitch, 1989, Genetics 122: 429-38). With respect to enhancement, +/+/+ < +/E(spl) < E(spl)/+/+ < E(spl)/E(spl), in accord with expectations from a hypermorphic allele; duplication for E(spl)+ achieved with Dp(3;3)M95A+16. In the absence of spl, E(spl) causes slight roughening of the eyes; furthermore, depending on parental constitution, varying percentages of embryos display defects in central- and peripheral-nervous-system development and irregular cuticular defects. A fraction of these fail to develop; percentages vary from 25% neural hypoplasia and 8% embryonic mortality in crosses between homozygous E(spl) parents to 100% death and 78% neural hypoplasia when both parents are E(spl)/Dp(3;3)M95A+. Both of these effects are sensitive to maternal genotype. That E(spl) is not simply a hypermorph is indicated by the fact that although +/Df(3R)Espl is viable, E(spl)/Df(3R)Espl is virtually lethal, especially when the deficiency is maternally inherited. Embryos homozygous for loss-of-function alleles vary in phenotype from weak to very strong neural hyperplasia, with concomitant aplasia of the epidermal sheath. Heterozygotes for stronger hypomorphic alleles may show terminal thickening of wing veins L4 and L5, and may have adventitious vein segments in the posterior wing membrane. Double heterozygotes for E(spl) loss-of-function alleles and either N or Dl are lethal. In the adult, increasing levels of E(spl) function result in increasing levels of split enhancement and in decreased numbers of sensilla as measured by the number of costal bristles on the wing. Conversely, decreased E(spl) function results in larger eyes and more sensilla plus ectopic sensory neurons appearing in the wing blade, especially along the posterior margin. Hemizygosity for E(spl)+ completely suppresses spl. Three doses of E(spl)+ increase the severity of the effects of the absence of function of Dl, reduce the severity of the absence of function of N, neu and mam and are without effect on the phenotype of bib-; conversely, absence of function of E(spl) is not affected by hyperploidy for any of the neurogenic loci or by loss of H function; from this De la Concha et al. infer that E(spl) is positively controlled by N and negatively controlled by H and Dl. Unlike the results using other neurogenic mutants, single vitally stained cells taken from the neurogenic ectoderm of E(spl)- embryos and transplanted into wildtype host embryos fail to give rise to clones containing epidermal cells; only neuronal elements are produced. This observation is interpreted to indicate that the E(spl)+ product serves a receptor rather than a signalling function (Technau and Campos-Ortega, 1987, Proc. Nat. Acad. Sci. USA 84: 4500-04).
Summary (Interactive Fly)
transcription factor - bHLH - Hairy/E(spl) class - neurogenic gene - target of Notch pathway - Casein kinase II regulates lateral-inhibition during eye and bristle development by targeting E(spl) repressors
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\E(spl)m8-HLH or the JBrowse view of Dmel\E(spl)m8-HLH for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Gene model reviewed during 5.42
Gene model reviewed during 5.48
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084961
769
179
Additional Transcript Data and Comments
Reported size (kB)
1.0 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0084335
20.3
179
9.14
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
179 (aa); 19.7 (kD predicted)
Comments
External Data
Subunit Structure (UniProtKB)
Homodimer (PubMed:22357926). Heterodimers with dpn (PubMed:22357926).Transcription repression requires formation of a complex with a corepressor protein (Groucho) (PubMed:8001118).
(UniProt, P13098)
Domain
The orange domain and the basic helix-loop-helix motif mediate repression of specific transcriptional activators, such as basic helix-loop-helix protein dimers. The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho, a transcriptional corepressor recruited to specific target DNA by Hairy-related proteins.
(UniProt, P13098)
Crossreferences
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\E(spl)m8-HLH using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (15 terms)
Molecular Function (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
Biological Process (9 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
Cellular Component (1 term)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

antennal anlage

Comment: reported as procephalic ectoderm anlage

central brain anlage

Comment: reported as procephalic ectoderm anlage

dorsal head epidermis anlage

Comment: reported as procephalic ectoderm anlage

visual anlage

Comment: reported as procephalic ectoderm anlage

endoderm

Comment: transiently expressed

antennal primordium

Comment: reported as procephalic ectoderm primordium

central brain primordium

Comment: reported as procephalic ectoderm primordium

visual primordium

Comment: reported as procephalic ectoderm primordium

dorsal head epidermis primordium

Comment: reported as procephalic ectoderm primordium

lateral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

ventral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

dorsal epidermis primordium

Comment: reported as dorsal epidermis anlage

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference

Comment: reference states 2-10 hr AEL

RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
E(spl) genes were found to be differentially expressed during metamorphosis. Unlike other E(spl) genes, E(spl)m8 maintains farily steady levels during metamorphosis.
The distribution of embryonic E(spl) transcripts was compared in D. melanogaster and D. hydei. The patterns of embryonic gene activity were found to be nearly indistinguishable. Mesectodermal expression was observed earlier in melanogaster embryos.
The peak of E(spl) expression during embryogenesis occurs at 2-10 hours. In the late blastoderm, expression is detected in a 2-3 cell-wide stripe on each side of the embryo, in groups of cells over the dorsal half of the poles, and abundantly in a dorsomedian band spanning the anterioposterior axis. During germ band extension, ectodermal expression is detected, and at the extended germ band stage, epidermal expression is abundant. In late stage 11, epidermal expression becomes patchy. At stage 10, the primordia of the supraoesophageal ganglion and the posterior midgut express E(spl). From stage 11 through late stage 12, expression is detected in the entire mesodermal layer. From late stage 11 through stage 14, expression is also detected in the primordia of the stomatogastric nervous system and in the optic lobes.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{m8-lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)m8-HLH in GBrowse 2
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 28 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 74 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of E(spl)m8-HLH
Transgenic constructs containing regulatory region of E(spl)m8-HLH
Deletions and Duplications ( 31 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
chordotonal organ precursor cell & ventral thoracic disc, with Scer\GAL4sca-109-68
macrochaeta | ectopic & scutellum, with Scer\GAL4455.2
microchaeta & mesothoracic tergum
scutum & macrochaeta, with Scer\GAL4ap-md544
scutum & macrochaeta, with Scer\GAL4h-1J3
scutum & microchaeta, with Scer\GAL432B
scutum & microchaeta, with Scer\GAL4ap-md544
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (13)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
4 of 15
Yes
No
4 of 15
Yes
No
3 of 15
No
No
3 of 15
No
No
 
2 of 15
No
Yes
2 of 15
No
Yes
 
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (12)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
5 of 15
Yes
No
4 of 15
No
No
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
No
2 of 15
No
Yes
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (11)
5 of 13
Yes
No
4 of 13
No
No
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
No
2 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (11)
4 of 12
Yes
Yes
2 of 12
No
No
1 of 12
No
Yes
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (27)
4 of 15
Yes
No
3 of 15
No
No
3 of 15
No
No
3 of 15
No
No
3 of 15
No
Yes
3 of 15
No
No
3 of 15
No
No
3 of 15
No
No
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (3)
5 of 15
Yes
No
1 of 15
No
Yes
1 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (1)
1 of 9
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 15
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190H0L )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila suzukii
Spotted wing Drosophila
Drosophila suzukii
Spotted wing Drosophila
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG09150CDN )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Lucilia cuprina
Australian sheep blowfly
Lucilia cuprina
Australian sheep blowfly
Lucilia cuprina
Australian sheep blowfly
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( None identified )
No non-Dipteran orthologies identified
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( None identified )
No non-Insect Arthropod orthologies identified
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( None identified )
No non-Arthropod Metazoa orthologies identified
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (12)
4 of 10
3 of 10
3 of 10
3 of 10
3 of 10
2 of 10
2 of 10
2 of 10
2 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Homodimer (PubMed:22357926). Heterodimers with dpn (PubMed:22357926).Transcription repression requires formation of a complex with a corepressor protein (Groucho) (PubMed:8001118).
    (UniProt, P13098 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-89
    Cytogenetic map
    Sequence location
    3R:26,040,240..26,041,008 [+]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    96F10-96F10
    Limits computationally determined from genome sequence between P{PZ}l(3)rQ197rQ197 and P{lacW}scribj7B3
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    96F11-96F14
    (determined by in situ hybridisation)
    96F8-96F13
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (22)
    Genomic Clones (22)
    cDNA Clones (6)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    BDGP DGC clones
      Drosophila Genomics Resource Center cDNA clones

      For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

      cDNA Clones, End Sequenced (ESTs)
      BDGP DGC clones
        Other clones
        RNAi and Array Information
        Linkouts
        DRSC - Results frm RNAi screens
        GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
        Antibody Information
        Laboratory Generated Antibodies
         
        Commercially Available Antibodies
         
        Other Information
        Relationship to Other Genes
        Source for database identify of
        Source for identity of: E(spl)m8-HLH E(spl)
        Source for database merge of
        Additional comments
        Other Comments
        dsRNA has been made from templates generated with primers directed against this gene. RNAi of E(spl) results in reduced arborization of ddaD and ddaE neurons, alterations in the number of MD neurons, defects in dendrite morphogenesis and reproducible defects in da dendrite development.
        CkIIα may regulate eye morphogenesis via phosphorylation of E(spl).
        Mutant allele fails to complement a QTL affecting male mating behaviour.
        Neither E(spl) nor Su(H) seem to be involved in the N pathway that directs the neuron/glia choice in the PNS.
        Enhancement of the Nspl-1 phenotype by E(spl)1 occurs within the remaining proneural cells, operating primarily at the protein level due to altered protein-protein interactions between E(spl)1 gene product and the proneural proteins.
        The distinct expression patterns of genes of the E(spl) complex in imaginal tissues depend to a significant degree on the capacity of their transcriptional cis-regulatory apparatus to respond selectively to direct proneural and Su(H)-mediated activation, often in a subset of the territories and cells in which proneural and Su(H) regulation is occurring.
        Candidate gene for quantitative trait (QTL) locus determining bristle number.
        Cells neighboring the SMC do not acquire the neural fate because N signalling pathway effectors, the HLH proteins of the E(spl) complex, block the sc self-regulation loop.
        Functional dissection of the E(spl) protein reveals E(spl) suppresses neural development by direct interaction with other proteins, such as gro and the proneural proteins.
        The bHLH domains of the gene products encoded by the E(spl)-C and AS-C differ in their ability to form homo- and/or heterodimers. The interactions established through the bHLH link the products of the two complexes in a single interaction network which may function to ensure that a given cell retains the capacity to choose between epidermoblast and neuroblast fates until the cell becomes definitively determined.
        Proneural and neurogenic genes control specification and morphogenesis of stomatogastric nerve cell precursors.
        Clones mutant for E(spl)-C bHLH-encoding genes or for gro display bristle hyperplasia. The E(spl)-C genes participate in the N signalling pathway. E(spl)-C mutants are epistatic over a gain of function mutant of N and ac-sc mutants are epistatic over E(spl)-C mutants. Expression in Schneider cells demonstrates HLHm5 and E(spl) mediate transcriptional repression of an ac Ecol\CAT reporter gene, gro potentiates this effect.
        Mutations show no interaction with high and low selection lines, abdominal and sternopleural bristle numbers are not affected. Results suggest E(spl) is not a candidate for bristle number quantitative trait loci (QTL) in natural populations or is in the same genetic pathway.
        Persistent expression of E(spl) and HLHm5 suppresses neural development.
        E(spl) functions in the N pathway in its role at the wing dorsoventral boundary.
        The genes of the E(spl) complex mediate only a subset of N activities during imaginal development. Comparisons of mutant phenotypes suggests that the N pathway bifurcates after the activation of Su(H) and that E(spl) activity is not required when the consequence of N function is the transcriptional activation of downstream genes. Transcriptional activation mediated by Su(H) and transcriptional repression mediated by E(spl) could provide greater diversity in the response of individual genes to N activity.
        The yeast interaction system has been used to study the E(spl) complex genes, results suggest that E(spl) and gro form a highly interconnected interacting network involved in transcriptional regulation.
        Almost all E(spl)-complex bHLH proteins can homo-hetero-dimerise, but not with the same efficiency. All E(spl)-complex bHLH proteins interact with gro protein via their C-terminal domain. E(spl)-complex bHLH proteins interact with proneural proteins, with members of the E(spl) family exhibiting distinct preferences for different proneural proteins.
        Proximal upstream region contains multiple specific binding sites for Su(H). Integrity of these sites and Su(H) activity are required not only for normal levels of E(spl) complex gene expression in imaginal disc proneural clusters but also for their transcriptional response to hyperactivity of the N receptor. Su(H) is a direct regulatory link between N receptor activity and the expression of E(spl) complex genes, extending the known lineage of the N cell-cell signaling pathway.
        The bristle loss phenotype of H mutants can be suppressed by deleting components of the E(spl)-complex. The degree of suppression depends on both the number and identity of E(spl)-complex transcription units removed.
        The E(spl) and ASC complexes interact with each other through the HLH domains of their components.
        Transcriptional repression by the h/E(spl) family of bHLH proteins involves two separable mechanisms: repression of specific transcriptional activators, such as sc, through the bHLH and orange domains and repression of other activators via interaction of the C-terminal WRPW motif with corepressors, such as the gro protein.
        E(spl) bHLH proteins are turned on in cells which are inhibited from becoming neural by signals from the delaminating neuroblast.
        In late stages of development E(spl) BHLH gene products are part of the same signalling pathway and are expressed in cells where N is activated. Loss of N function leads to a reduction in E(spl) bHLH protein expression and the presence of ubiquitous activated N result in high levels of E(spl) bHLH throughout the developing wing disc, effects are independent of genes of the AS-C.
        E(spl) protein expression in ectodermal cells commences in the neuroectoderm when neuroblasts have began to delaminate.
        Experiments with a chimeric E(spl) derivative with a heterologous transcriptional activation domain support the idea that E(spl) proteins normally act as direct repressors of transcriptional activation of regulatory genes, possibly including the ASC genes.
        Gel retardation experiments demonstrate the 5' regulatory region from position -1166 to +87 contains in vitro binding sites for Su(H).
        E(spl) complex basic helix loop helix genes inhibit neural fate during the selection of neural precursors, and play a role in restricting the neuronal fate to one of the four progeny cells of the bristle precursor.
        N signalling activity is directly responsible for the accumulation of basic helix-loop-helix proteins encoded by the E(spl) locus.
        The gene products of ac, sc and l(1)sc together with vnd act synergistically to specify the neuroectodermal E(spl) and HLHm5 expression. Negative cross- and autoregulatory interactions of the E(spl) complex contribute, directly or indirectly tot he regulation.
        DNaseI footprinting analysis of bacterially expressed E(spl) and HLHm5 demonstrates the gene products can bind as homo- and heterodimers to a sequence in the promoters of the E(spl) and ac genes, called the N-box, which differs slightly from the consensus binding site for other bHLH proteins.
        Electrophoretic mobility shift assays demonstrate that E(spl) is directly activated in proneural clusters of the late third-instar wing imaginal disc by protein complexes that include the ac and sc bHLH proteins.
        E(spl) is a neurogenic gene required initially to ensure the correct number of PNS precursors. E(spl) is not required for the late epidermal maintenance function.
        Arrangement and sequence of E(spl)-complex genes in D.melanogaster and D.hydei revealed that the E(spl)-gene, and the structure of complex are highly conserved, suggesting that each individual gene, as well as the organization of the complex, is of functional importance.
        E(spl) complex gene expression pattern in N and neur mutants suggests the protein is required in dictating cell fates during embryogenesis.
        Conclusion based on interactions with Df(3R)E(spl)-rv27, as opposed to point mutations in E(spl) locus.
        NM1 defines a new class of Notch allele: similarity with and lack of specificity of interaction of N- and NM1 with H, mam, gro and E(spl) suggest that the NM1 effect is due to modification in the intracellular signalling of the activated N receptor.
        On basis of cross-hybridization and sequence data the E(spl) HLH genes can be placed into 3 groups. The first includes E(spl) and HLHm5, the second includes HLHm7, HLHm3, HLHmA and HLHmB and the last includes HLHmC.
        The embryonic phenotype of neurogenic mutations was examined in most tissues using Ecol\lacZ enhancer trap lines. All alleles examined show defects in many organs from all three germ layers. At least for ectodermally and endodermally derived tissues, neurogenic gene function is primarily involved in interactions among cells that need to acquire or maintain an epithelial phenotype.
        Genes of the E(spl) complex act as a functional unit composed of redundant genes which can partially substitute for each other. Eight E(spl)-region genes are required for the development of neurectodermal cells: HLHmδ, HLHmβ, HLHmγ, HLHm3, HLHm5, HLHm7, E(spl) and gro. The E(spl)-region gene m4 may also play a role in this process.
        E(spl) acts in the last step of lateral inhibition (de la Concha, Genetics 111: 499--508) and the E(spl) region encodes several HLH proteins (Klambt, EMBO J. 8: 203--210).
        In vitro DNA binding assays demonstrate that the basic domain of the E(spl) gene product is necessary for DNA binding. Dominant enhancement of Nspl-1 is caused by the truncation of the E(spl)1 protein in combination with a deletion of a putative regulatory element.
        E(spl) is needed for proper mesoderm differentiation prior to the onset of nau expression: mutant alleles cause hypertrophy in nau expressing cells.
        The neurogenic phenotype of various embryonic combinations have been studied and include extreme neurogenic embryos, moderate extreme embryos, intermediate neurogenic embryos, weak intermediate neurogenic embryos and weak neurogenic embryos.
        Genetic analysis demonstrates that Dl, neu, E(spl), HLHm5, HLHm7 and m4 are functionally related. Spatial distribution of mRNA in neurogenic mutant embryos suggests that some of the functional interactions take place at the transcriptional level.
        Ecol\lacZ reporter gene constructs demonstrate that neurogenic loci are required to restrict the number of competent cells that will become sensory mother cells, SMCs.
        A synergistic interaction is observed between E(spl) and emc alleles with regard to the ectopic posterior macrochaetae.
        E(spl)- cells fail to differentiate chaetae in the step of sensory organ mother cell singularization and/or later during epidermal sublineage specification.
        DNA sequence analysis reveals four E box binding sites, for the binding of hetero-oligomeric complexes composed of da or AS-C proteins, in the first 877 bp of the ac upstream region. Electrophoretic mobility shift assays demonstrate that the emc protein can specifically antagonise DNA binding of the da/AS-C complexes in vitro in a dose-dependent manner, h and E(spl) proteins fail to exhibit this inhibitory effect.
        E(spl) mutations show no interaction with dx.
        Genetic analysis demonstrates that Dl mutations can modify the imaginal phenotypes that result from heterozygosity for E(spl) mutations.
        The Notch phenotypic group includes neurogenetic mutations involved in cell communications. Some alleles are embryonic lethal.
        Transcription unit m8 is essential for normal E(spl) function.
        N, Dl and E(spl) gene products interact directly during embryonic and imaginal development. Morphogenesis of the ectodermally derived adult eye is sensitive to the combined action of the N, Dl and E(spl) gene products.
        A study of the interactions between N, Dl, H and E(spl) suggest that the effects of H, Dl and E(spl) on N are allele specific and occurring at the protein level.
        Neural hyperplasia, caused by mutations in E(spl), can be prevented by the presence of another neurogenic mutation.
        Molecular and cytogenetic analysis of the E(spl) locus has led to the characterization of a 14kb deletion that affects E(spl) functions.
        The genetic organization of the chromosome interval 96F8 has been determined. Results suggest that several genetic functions are related to E(spl) and that the role E(spl) plays in neurogenesis requires the participation of more than one of these genetic functions.
        Dl- phenotype increases in severity in the presence of triploidy for E(spl), the N- and neur- phenotypes decrease in severity. This relationship is not reciprocal.
        Mutant analysis of E(spl) indicates that low levels of E(spl)+ gene activity result in hyperplasia of both the CNS and PNS, fewer neurons are produced in genotypes where the activity of the locus has increased. Results suggest that E(spl) acts as a genetic switch directing the decision to become either a neural or epidermal progenitor.
        Regions of E(spl) cross-hybridize to the opa sequence.
        E(spl) mutants display no ventral cuticle and hypertrophy of the central nervous system.
        Locus involved in the differentiation of the neural ectoderm into neuroblasts and epidermoblasts. Increased levels of gene product favor epidermal differentiation, whereas decreased levels favor neuronal differentiation. Locus originally identified by the split-enhancing feature of a dominant gain of function mutation. Loss of function mutations are lethals and are described separately. E(spl) causes spl/+ to display a split phenotype and elicits a more extreme phenotype in spl/spl and spl/Y. The spl-enhancing effect of E(spl)1 is suppressed in flies heterozygous for Dl (Shepard et al., 1989). With respect to enhancement, +/+/+ < +/E(spl) < E(spl)/+/+ < E(spl)/E(spl), in accord with expectations from a hypermorphic allele; duplication for E(spl)+ achieved with Dp(3;3)M95A+16. In the absence of spl, E(spl) causes slight roughening of the eyes; furthermore, depending on parental constitution, varying percentages of embryos display defects in central- and peripheral-nervous-system development and irregular cuticular defects. A fraction of these fail to develop; percentages vary from 25% neural hypoplasia and 8% embryonic mortality in crosses between homozygous E(spl) parents to 100% death and 78% neural hypoplasia when both parents are E(spl)/Dp(3;3)M95A+16. Both of these effects are sensitive to maternal genotype. That E(spl) is not simply a hypermorph is indicated by the fact that although heterozygous E(spl)- deletions are viable, hemizygous E(spl) is virtually lethal, especially when the deficiency is maternally inherited. Embryos homozygous for loss-of-function alleles vary in phenotype from weak to very strong neural hyperplasia, with concomitant aplasia of the epidermal sheath. Heterozygotes for stronger hypomorphic alleles may show terminal thickening of wing veins L4 and L5 and may have adventitious vein segments in the posterior wing membrane. Double heterozygotes for E(spl) loss-of-function alleles and either N or Dl are lethal. In the adult, increasing levels of E(spl) function result in increasing levels of split enhancement and in decreased numbers of sensilla as measured by the number of costal bristles on the wing. Conversely, decreased E(spl) function results in larger eyes and more sensilla plus ectopic sensory neurons appearing in the wing blade, especially along the posterior margin. Hemizygosity for E(spl)+ completely suppresses spl. Three doses of E(spl)+ increase the severity of the effects of the absence of function of Dl, reduce the severity of the absence of function of N, neu and mam and are without effect on the phenotype of bib-; conversely, absence of function of E(spl) is not affected by hyperploidy for any of the neurogenic loci or by loss of H function; from this De la Concha et al. infer that E(spl) is positively controlled by N and negatively controlled by H and Dl. Unlike the results using other neurogenic mutants, single vitally stained cells taken from the neurogenic ectoderm of E(spl)- embryos and transplanted into wild-type host embryos fail to give rise to clones containing epidermal cells; only neuronal elements are produced. This observation is interpreted to indicate that the E(spl)+ product serves a receptor rather than a signalling function (Technau and Campos-Ortega, 1987).
        Origin and Etymology
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        NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
        GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
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        BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
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        Synonyms and Secondary IDs (32)
        Reported As
        Symbol Synonym
        E(spl)m8
        (Wissel et al., 2018, Shukla et al., 2017, Wu et al., 2017, Zaytseva and Quinn, 2017, Auer et al., 2015, Parsons et al., 2014, Tseng et al., 2014, Vuong et al., 2014, Zhang et al., 2014, Babaoğlan et al., 2013, Christiansen et al., 2013, Djiane et al., 2013, Schaaf et al., 2013, Woodfield et al., 2013, Zhou and Luo, 2013, Legent et al., 2012, Ulvklo et al., 2012, Zacharioudaki et al., 2012, Abed et al., 2011, Barry et al., 2011, Di Stefano et al., 2011, Duan et al., 2011, Endo et al., 2011, Wang et al., 2011, Bernard et al., 2010, Kugler and Nagel, 2010, Ngo et al., 2010, Herz et al., 2009, Krejcí et al., 2009, Lee et al., 2009, Li et al., 2009, Moshkin et al., 2009, Schaaf et al., 2009, Kaspar et al., 2008, Parks et al., 2008, Ayyar et al., 2007, Kugler and Nagel, 2007, Childress et al., 2006, Childress et al., 2006, Herz et al., 2006, Castro et al., 2005, Lai et al., 2005, Zarifi et al., 2005, Bianchi-Frias et al., 2004, Kamimura et al., 2004, De Joussineau et al., 2003, Klein, 2003, Koelzer and Klein, 2003, Villa-Cuesta et al., 2003, Lai, 2002, Negeri et al., 2002, Rosenberg and Parkhurst, 2002, Ledent and Vervoort, 2001, Nolo et al., 2000, Ligoxygakis et al., 1999, Fisher and Caudy, 1998, Lai et al., 1998, Liang and Biggin, 1998, Schweisguth and Lecourtois, 1998, Kim et al., 1997, Lai and Posakony, 1997, Sotillos et al., 1997, Barbash and Cline, 1995, Dawson et al., 1995, Furukawa et al., 1995, Singson et al., 1994, Ishibashi et al., 1993, Wainwright and Ish-Horowicz, 1992, Garrell and Campuzano, 1991, van Doren et al., 1991, Vaessin et al., 1990)
        anon-EST:Liang-1.71
        l(3)96Fd
        m8
        (Singh et al., 2019, Bivik et al., 2016, Kiparaki et al., 2015, Kux et al., 2013, San Juan et al., 2012, Yamakawa et al., 2012, Zarifi et al., 2012, Cave et al., 2011, Bardin et al., 2010, Bernard et al., 2010, Vachias et al., 2010, Chanet et al., 2009, Maeder et al., 2009, Moshkin et al., 2009, Rand et al., 2008, Eastman et al., 2007, Goodfellow et al., 2007, Krejci and Bray, 2007, Brody et al., 2006, LeComte et al., 2006, Zinzen et al., 2006, Cave et al., 2005, Giagtzoglou et al., 2005, Kan and Kessler, 2005, Levine and Davidson, 2005, Macdonald and Long, 2005, Macdonald et al., 2005, Schlatter and Maier, 2005, Stathopoulos and Levine, 2005, Nagel et al., 2004, Secombe and Parkhurst, 2004, Jafar-Nejad et al., 2003, Cowden and Levine, 2002, Kumar and Moses, 2001, Kumar and Moses, 2001, Trott et al., 2001, Klein et al., 2000, Kumar and Moses, 2000, Lai et al., 2000, Wesley and Saez, 2000, Govind, 1999, Nagel and Preiss, 1999, Nagel et al., 1999, Nellesen et al., 1999, Wech et al., 1999, Wesley, 1999, Wurmbach et al., 1999, zur Lage and Jarman, 1999, Ligoxygakis et al., 1998, Ligoxygakis et al., 1998, Nagel and Preiss, 1997, Preiss et al., 1997, de Celis et al., 1996, Gigliani et al., 1996, Heitzler et al., 1996, Alifragis et al., 1995, Alifragis et al., 1995, Lecourtois and Schweisguth, 1995, Lecourtois and Schweisguth, 1995, Tepass and Hartenstein, 1995, Tata and Hartley, 1993, Tietze et al., 1993, Delidakis and Artavanis-Tsakonas, 1992, Fischer-Vize et al., 1992, Tietze et al., 1992, Knust et al., 1991, Preiss et al., 1991, Schrons et al., 1991, Campos-Ortega and Knust, 1990, Campos-Ortega and Knust, 1990, Klambt et al., 1989, Knust et al., 1987)
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