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FB2025_05,released December 11, 2025
DER, top, flb, Elp, dEGFR
transmembrane receptor tyrosine kinase for signaling ligands in the TGFα family (Gurken, Spitz, Vein, and Keren) - utilises the intracellular MAP kinase pathway - during oogenesis helps set up egg polarity, determines the identity of cells in the ectoderm - during larval stages participates in the development of the eye and wing - regulates growth, cell survival and developmental patterning
Please see the JBrowse view ofDmel\Egfr for information on other features
To submit a correction to a gene model please use theContact FlyBase form
AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.51
7.6, 7.1 (northern blot)
None of the polypeptides share 100% sequence identity.
175 (kD)
Homodimer (PubMed:19718021,PubMed:20723758). Binding of the ligand spitz triggers homodimerization of the receptor however, it is able to form dimers, albeit weakly, in the absence of spitz (PubMed:19718021,PubMed:20723758). Interacts (when phosphorylated on tyrosine residues) with Vav (via SH2 domain) (PubMed:10781813). Interacts (when ubiquitinated) with Graf (PubMed:28993397). May interact (when phosphorylated) with EGFRAP (via SH2 domain) (PubMed:34411095).
Ubiquitination by Cbl in response to high spi, promotes its interaction with Graf and thus facilitates its GPI-enriched endocytic compartment (GEEC) mediated endocytosis and its subsequent degradation.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Egfr using theFeature Mapper tool.
The testis specificity index was calculated from modENCODE tissue expression data byVedeleket al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:anlage in statu nascendi
Comment:reported as procephalic ectoderm anlage in statu nascendi
Comment:reported as procephalic ectoderm anlage in statu nascendi
Comment:reported as procephalic ectoderm anlage in statu nascendi
Transcript is detected in a subset of the longitudinal glia in the ventral midline.
Egfr transcripts are distributed uniformly in the undifferentiated part of the eye-antennal disc from the antennal disc to in or slightly ahead of the morphogenetic furrow. They are also detected in the larval optic lobe in a pattern similar to the protein distribution.
Egfr transcripts are first observed in the late syncytial blastoderm embryo and increase substantially during cellularization. In gastrulating embryos, signal is higher in the ectoderm than in the endoderm or mesoderm and the strongest expression is seen in the cephalic furrow. During germ band extension,Egfr transcripts continue to be detected in the ectoderm and in the mesoderm. As the neuroblasts segregate, expression is missing in the neuroblast layer but is seen as two stripes along the germ band in the ectoderm and in the meso erm. In the later part of germ band extension, expression is detected in the stomodeum, the clypeo-labrum, and in the gnathal segments.Egfr is therefore found in all primordial tissues of the mouthparts and foregut. At stage 14, expression is observed in the region where the posterior spiracles and the telson will form. From stage 14 on, expression is observed in the ventral midline of the CNS. In stages 15 and 16, expression is observed along the entire periphery of the midgut. At stage 17, the most prominent regions of expression include the internal part of the proventriculus, the epit elium of the pharynx, and the fat body. In third instar larvae, expression is observed in imaginal discs. Expression is not evenly distributed among the discs or in a single disc. For example, in the eye disc, expression is abundant and uniform anterior to the morphogenetic furrow but posterior to the furrow is only found in the basal portion of the disc. Expression in the discs is observed in the epithelium but not in the adepithelium.Egfr is also expressed unevenly in developing ovaries and is detected in restricted regions of the CNS. Expression is observed in the inner and outer proli eration centers and in cells of the developing optic lamina. In addition, expression is found in a subset of polytene larval tissues including the valvular epithelium of the proventriculus and the fat body. Low levels of expression are seen in the salivary glands and in a subset of cells in the Malphigian tubules. The larval pattern of expression continues into prepupae. In early pupae, expression continues in the disc epithelia, the optic lamina, and fat body. Weak expression is also observed around each ovarian egg chamber. Later in the pupal period, expression declines in the midgut epith lium and is observed in the fore- and hindguts.Egfr expression in adults is mainly restricted to three types of tissues; imaginal fat body, valvular epithelium of the proventriculus, and the follicular epithelium of the ovary.
Egfr transcripts are observed in the periphery of cellular blastoderm embryos and persist at least until ventral furrow formation. In larvae, transcripts are observed in all imaginal discs and in subsets of cells within the cortex of the brain but not in the salivary glands. The expressing cells in the brain are thought to correspond to the proliferative centers. This pattern is consisten withEgfr expression preferentially in mitotically active cells. In ovaries, expression is observed in the vitellogenic follicle cells in young egg chambers. Follicle cells surrounding more mature oocytes no longer have higher levels ofEgfr than the surrounding cells. Some transcript is also found in nurse cells and in the oocyte. In adults, someEgfr transcript is observed in males and females in tissues other than the ovary showing that someEgfr is expressed in nonproliferating cells in adults.
Egfr transcripts were found to be uniformly distributed in 10-14hr embryos and in 24hr embryos. In larvae, transcripts are uniformly distributed in the brain cortex, the anlagen of the ovaries and testes and in imaginal discs including the eye-antennal, wing, and genital discs. In adults, transcripts are localized in the cortex of the brain and in the thoracic and abdominal ganglia.
Egfr transcripts are detected at all stages of development tested. They are expressed at high levels in embryos and at reduced levels in larvae and pupae. In adults the 7.6kb transcript is much less abundant than the 7.1kb transcript.
In eye imaginal discs, the highest levels ofEgfr protein are found anterior to the morphogenetic furrow. Just posterior to the furrow, the levels are sharply reduced in cells not recruited into the ommatidia but remain high in photoreceptor precursor cells. In the posterior of the eye disc the pattern is reversed. Levels are low in the ommatidia and highest in the surrounding undifferentiated cells that will become pigment and bristle nerve cells.
Egfr protein is detected in wholemount imaginal discs in a relatively uniform distribution. In eye discs, protein is observed in the furrow and anterior to the furrow but not posterior to the furrow. In sectioned discs,Egfr protein appears to be limited to the apical microvillar border of the eye disc epithelium anterior to and within the furrow. Staining is also observed in the presumptive larval optic lobes in the lateral and outer proliferation centers of the lamina. Finally, staining is seen along the midline of the ventral nerve cord.
Egfr protein is widely distributed throughout the cellular blastoderm embryo. It appears to be localized at the periphery of cells in the newly formed plasma membranes. During gastrulation, it is expressed in all ectodermal epithelial cells. In germ band extended embryos, it continues to be expressed in the ectoderm and is also expressed in the newly formed mesodermal cell layer. Intense staining in the head is also observed particularly in the mandibular bud, the procephalic lobe, and the clypeolabrum. In germ band retracted embryos, staining is observed in the epidermis at the tip of the clypeolabrum and in the epithelium of the terminal portion of the hindgut. Epidermal staining is also seen in the segmental grooves.Egfr staining is pronounced in germ band retracted embryos at the sites of somatic muscle attachments where it localizes particularly to the tendon cells at the ectodermal epithelial aspect of the apodemes. Most splanchnic mesodermal derivatives expressEgfr. Staining is apparent in the fat body and in the visceral musculature. Finally, staining is pronounced in the ventral midline of the CNS.
JBrowse - Visual display of RNA-Seq signals
ViewDmel\Egfr in JBrowse
2-95
2-102.1
2-99
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
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 seeJBrowse for alignment of the cDNAs and ESTs to the gene model.
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.
polyclonal
New stable cell line derived fromS2-unspecified : Stable cell lines that express the full lengthspi protein (designated S2:spi ) or a truncated, secreted form ofspi protein (designated S2:sspi ) were created. Stable cell lines that expressEgfr were created and designated S2:DER1b and S2:DER2f . The S2:DER2f cell line is a constitutiveEgfr-expressing cell line that was subsequently called D2F.
New stable cell line derived fromS2-unspecified : Stable cell lines were generated starting from a S2+ line that stably expressesEgfr. This line was stably transformed with full length or mutantPtp10D.
Identified as a candidate gene for hypoxia-specific selection (via an experimental evolution paradigm) that is also differentially expressed between control and hypoxia-adapted larvae.
Egfr negatively regulates apoptosis in the amnioserosa.
Egfr signalling controls compartment size in embryos.
Egfr signalling defines a protective function for ommatidial orientation in the eye.
A survey of association between 267 SNPs in almost 11kb of theEgfr gene and the degree of eye roughening due to a gain-of-functionEgfrE1 allele crossed into 210 isogenic wild-type lines provides evidence that a handful of synonymous substitutions supply cryptic variation for photoreceptor determination.
Egfr signalling regulates ommatidial rotation and cell motility in the eye.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
Egfr in the peripodial membrane, mediates the role of the peripodial membrane in subdivision of the wing disc into presumptive wing and notum (mesothoracic tergum).
Egfr activation is required for progression from G2 to M phase in the second mitotic wave cells in the developing eye disc.
Egfr has a role in ommatidial spacing in the eye.
ExcessEgfr signalling can overrule lateral inhibition in the proneural cluster and allow adjacent cells to become SMCs and sensory organs.
Egfr activation in cyst cells may send a signal that prevents self-renewal of stem cell identity by the germ cell they enclose.
Eleven EMS induced alleles were identified in a screen for mutations affecting commissure formation in the CNS of the embryo.
Egfr interacts synergistically withwg to promote tergite and sternite identities in the adult abdomen, andEgfr andwg activities are opposed bydpp signalling which promotes pleural identity.wg anddpp compete directly by exerting opposite effects on cell fate. Within the tergite, the requirements ofwg andEgfr function are complementary:wg is required medially, whereasEgfr is most important laterally.
The femoral chordotonal organ arises from a cluster of sensory organ precursors (SOPs).N signalling is required to limit SOP commitment in the development of this cluster, but does not prevent multiple SOP formation because of the antagonistic action ofEgfr signalling.Egfr signalling is required for clustering, promoting SOP commitment rather than proliferation or protection from cell death.
Egfr signalling is required for the differentiation and maintenance of neural progenitors along the dorsal midline of the embryonic head.
Egfr activity is both necessary and sufficient for cartridge neuron assembly.
Egfr signalling promotes the 2o/3o pigment cell fate at the expense of programmed cell death in the interommatidial lattice.
Mutant eye phenotype suggestsEgfr is involved in early aspects of ommatidial spacing, which presumably contributes to the overall roughness phenotype.
Immediately after the movement of the oocyte nucleus to the future dorsal pole a broad activation of theEgfr pathway takes place. As a result, all follicle cells, except the ventral-most rows, expressEgfr-target genes. After completion of cell migration, transcription ofrho in the dorsal-anterior follicle cells is achieved by activation of theEgfr pathway, in conjunction with signals that may emanate from the anterior, stretch follicle cells. Ectopic activation ofrho in the stretch follicle cells can lead to activation of theEgfr pathway in the follicle cells covering the oocyte. Results suggest thatrho is responsible for triggering the production or processing of aEgfr ligand that is expressed in the follicle cells. Genetic interaction studies suggest theS gene may participate inEgfr signalling in the ovary.
TheEgfr product promotes the formation, patterning and individual fate specification of early forming neuroblasts along the dorso-ventral axis of the embryo.Egfr signalling functions help specify the fate of medial neuroblasts and to promote neuroblast formation in the intermediate column.Egfr signalling is dispensable for the development of lateral column neuroblasts.
Egfr activity is essential for establishing the first ommatidial cell fate, the R8 photoreceptor neuron.
Egfr signalling plays an instructive role in CNS patterning and exerts differential effects on dorsoventral subpopulations of neuroblasts.
Sequential activation, amplification and local inhibition of theEgfr receptor forms an autoregulatory cascade that leads to the splitting of an initial single peak of signalling into two, patterning the dorsal egg.
Egfr is required to repress transcription of proneural genes and to promote neuroblast formation in the intermediate column of the neurectoderm.
Genetic combinations with mutants ofnub cause additive phenotypes.
In the developing eye disc ofEgfr mutant larvae the vast majority of cells fail to be recruited into preclusters and behave like nonrecruited cells, they undergo S phase and arrest in the following G2 phase. Only a minor fraction of the cells are released into mitoses to be recruited into developing ommatidia. Ectopicstg expression allows G2 arrested postfurrow cells to enter mitosis.
Shows no genetic interaction withsdk.
Egfr appears to be required for the initial determination of the correct midline glial cell number, as well as for further midline glia differentiation.
Phylogenetic analysis of the PTK family.
Signalling by theEgfr protein is critical for cell fate specification in the ventral cuticle of the Drosophila larva: this signalling pathway is required and apparently sufficient to specify row 1-4 denticles in the abdominal belts. To specify these denticles, signalling by theEgfr protein antagonises signalling by thewg protein in cells of the prospective row 1-4 zone.
Study of expression and function of different components of theN pathway in both the wing disc and pupal wings proposes that the establishment of vein thickness utilises a combination of mechanisms. A mechanisms includes repression ofrho transcription byHLHmβ and maintenance ofDl expression byrho/Egfr activity.
The role ofEgfr in chordotonal precursor formation is characterised.
The primary target genes ofEgfr arepnt,vnd andFas3, these are induced in different ectodermal domains. Secondary target genesoc,argos andtrn are activated bypnt in response toEgfr signalling. The proper induction of these genes requires the concomitant inactivation ofaop, mediated byEgfr signalling.
The function ofspi,rho andS appears to be non-autonomous; expression of the precursor only in the midline is sufficient for patterning the ventral ectoderm. Facilitating the expression ofspi,rho andS is the onlysim-dependent contribution of the midline to patterning the ventral ectoderm, since the mutantsim ectodermal defects can be overcome by expression of secretedspi in the ectoderm. These results suggest a mechanism for generating a graded distribution of secretedspi, which may subsequently give rise to graded activation ofEgfr in the ectoderm.
Egfr receptor is involved in the differentiation of a large subset of embryonic somatic muscles and their precursors. Temperature sensitive alleles ofEgfr demonstrate the mesodermal function of the gene is required in the late extended germ band stage subsequent to its requirement in the ectoderm.spi group genes have a similar phenotype, loss of multiple mature muscles and their precursors.
In vitro fusion of the homologous extracellular domain ofEgfr andGlt to theNrt cytoplasmic domain can mediate aggregation of cells incubated with a soluble crude fraction containgNrt ligand activity. The binding site for theNrt ligand is localised within the extracellular domain. A stretch of 25 amino acids forms an alpha-helix located close to the pseudocatalytic site and is crucial for the adhesive function.
Mutations in components of theEgfr signalling pathway dominantly effect penetrance of thechic crossvein phenotype.Egfr is proposed to be an activator in longitudinal vein formation. There is a distinct signalling pathway activated byEgfr that interacts withRas85D signal transduction cascade to induce crossvein formation in the wing that might be used for signalling processes elsewhere in the developing fly.
Thespi product triggers theEgfr signaling cascade. Graded activation of theEgfr pathway may normally give rise to a repertoire of discrete cell fates in the ventral ectoderm and graded distribution ofspi may be responsible for the graded activation. Therho andS products may act as modulators ofEgfr signaling. Epistatic relationships suggest thatrho andS may normally facilitate processing of thespi precursor.
Mutations can act as dominant modifiers of the activatedN eye phenotype (FBrf0064452).
Activation of theEgfr pathway during oogenesis is not sufficient to specify dorsal fate when activated ectopically.
Molecular analysis of mutant alleles reveals an intriguing correlation between molecular lesions and mutant phenotypes. Alleles that specifically affect specific processes encode receptors with altered extracellular domains. Alleles that fully or partially complement a wide range of embryonic and postembryonic phenotypes encode receptors with altered intracellular domains. These findings suggest that theEgfr protein may be activated by tissue specific ligands, that theEgfr receptor tyrosine kinase may phosphorylate multiple substrates, that signal transduction byEgfr requires the physical association of substrates and that the extracellular domain of theEgfr protein may play an essential role in mediating receptor-receptor interactions.
Egfr requirement for Malpighian tubule development is during the period of cell division.
Mutations inEgfr affect the development of the Malpighian tubules, final cell number is reduced. The two pairs of tubules are affected to a different extent.
Displays epistatic interactions withsqd alleles.
Observations of mutants support the proposal that axon fascicles can make at least some pathfinding decisions independently of their neighbours.
Molecular analysis of grk suggests that it is the Egfr ligand functioning in the female germline in dorsoventral patterning.
Egfr gene product is essential for determining the identity of cells within the ventral ectoderm.
Double mutant analysis indicates that ve acts upstream of Toll in dorsal-ventral axis formation, and the action of ve requires the grk-Egfr signaling pathway.
Egfr is required for normal cell proliferation in all imaginal discs.Egfr- cells in the eye disc are unable to differentiate as photoreceptor cells. Clonal analysis of cells carrying both loss of function and gain of functionEgfr mutations indicates that, in either case, cells are more likely to differentiate as photoreceptors if they are in contact with cells of lowerEgfr activities.
Mutations affect eye morphology.
Double mutant brn;Egfr mothers lay strongly ventralised eggs.
Egfr protein expression in third instar larval imaginal discs has been determined.
Egfr RNA expression during development has been studied.
The phenotype of heteroallelic combinations of a large number ofEgfr mutations has been studied.
Mutations at the Egfr locus cause defects in midoogenesis.
Zygotically active locus involved in the terminal developmental program in the embryo.
TheEgfr protein is glycosylated and is located in the plasma membrane.
Germ line mosaic analysis demonstrates that theEgfr gene product is required in the somatic cells for chorion patterning and dorsoventral patterning of embryonic cells.
Egfr has been isolated and characterised, the protein has three functional domains similar to the human EGF receptor.
In situ hybridisation has revealed a unique growth factor that binds both insulin and epidermal growth factor (EGF) and is antigenically related to the EGF receptor of mammals.
Encodes the Drosophila homolog of epidermal growth factor receptor protein. Mutations with three different phenotypes and described under three different names shown to be alleles of Egfr. Elp (Ellipse) is a dominant eye shape and texture mutant; flb (faint little ball) is an embryonic lethal causing dorsalized embryos, and top (torpedo) is a maternal-effect lethal causing ventralized embryos. Ellipse alleles are dominant (hypermorphic) mutations of Egfr.EgfrE1 in heterozygous combination with a deficiency or null mutation for Egfr is normal in phenotype. Eyes ofEgfrE1/+ heterozygotes rough and more oval than wild type; also display a slight disturbance of the wing-vein pattern. Homozygotes have smaller eyes with many fewer ommatidia and some regions lack them entirely; those ommatidia that are formed contain the normal number and arrangement of cells; the regions without ommatidia contain cells that resemble pigment cells and mechanosensory bristles; only about one tenth the normal number of preommatidial cell clusters differentiate behind the morphogenetic furrow. faint little ball alleles (Egfrf) are recessive embryonic lethal alleles of Egfr that lack a maternal effect (as shown by pole cell transplantation). Embryos form a ball of dorsal hypoderm with the internal organs extruded anteriorly. Ventral cuticle absent or strongly reduced. First visible in extended-germ-band stage. Cells at the anterior and posterior ends of the embryo form clumps and slough off; very few head and gnathal cells remain. Substantial ectodermal cell death observed; germ band retraction fails to take place. Ultimately, cuticle formation produces mostly dorsal and lateral cuticular elements with but a narrow strip of denticles midventrally. Hypomorphic alleles initiate but do not complete germ-band retraction; they show intermediate phenotypes with wider denticle bands and in weak alleles some head and telson structures are formed as well. torpedo alleles (Egfrt) are maternal effect lethals. Maternal-effect lethal. Homozygous females lay eggs that are long and pointed at both ends. Such eggs often have only one fused dorsal appendage; also there is an increase in the number of follicle cells that give rise to the main body of the chorion at the expense of those ordinarily contributing to the operculum and dorsal appendages. "Egfrt" alleles are completely recessive and fully penetrant in homozygous females; the embryos never hatch. Homozygous and hemizygous adult flies exhibit incomplete fourth veins, absence of the anterior crossvein, rough eyes, loss of ocelli and ocellar bristles and the loss of sensory bristles from the thorax. Changes in the embryonic pattern become visible at the beginning of gastrulation. Around the circumference of the embryo, 40% of the cells invaginate on the ventral side and form mesoderm; these cells become organized into two ventral furrows which are lost in later stages and a mass of mesodermal cells fills the ventral half of the embryo. The only cuticle structure differentiated is a strip of dorsal hypoderm flanked by bands of ventral setae; lateral and ventral sides are made up of mesoderm. The head is reduced but filzkorper and spiracles are visible posteriorly. Experiments with germ-line mosaics produced by pole cell transplantation indicate that the mutant gives rise to ventralized eggs and embryos by interfering with processes taking place in somatic cells rather than germinal tissue. The mutant phenotype was only produced in mosaics in which wild-type germ cells were surrounded by Egfrt follicle cells and not by the reverse cell arrangement. Egfrt blocks dorsalization caused by fs(1)K10, but not that produced by dl females. In situ hybridization with transcript-specific probes reveals uniform distribution of transcript during embryogenesis; in larvae, hybridization confined to mitotic tissues and not seen in cells with polytene chromosomes (Kammermeyer and Wadsworth, 1987). Transcript concentrated in cells of the central nervous system and gonial cells in adults.
Source for merge of: Egfr l(2)05351
Identified by PCR fragment; relationship to other protein tyrosine kinase genes not known.
Identified by PCR fragment; relationship to other protein tyrosine kinase genes not known. Price, Clifford and Schupbach (1989) subsumed the embryonic lethal alleles (flb) under the symbol for the maternal-effect-lethal alleles (top). Lindsley and Zimm (1992) further consolidated both along with the dominant visible alleles (Elp) under the symbol Egfr as "Egfrf", "Egfrt" and "EgfrE" alleles respectively.
