Epidermal growth factor receptor

Epidermal growth factor receptor (EGFR)

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Symbol: AKA: EGFR; Drosophila EGF receptor (DER) {Links}	Flybase ID: {Flybase_ID}
Synonyms: {Name}	{GadFly}
Function: {Short_Function}	{LocusLink}
Keywords: {Keywords}	{Interactive_Fly}

{Summary}

Function/Pathway

Vn/EGFR signaling directs cells to become notum by antagonizing wing development and by activating notum-specifying genes (Wang, 2000)
Vn/EGFR signaling directs cells to become part of the dorsal compartment by induction of apterous and consequently also controls wing development, which depends on an interaction between dorsal and ventral cells (Wang, 2000)
Activated by small signalling molecules, all characterised by having one EGF-like motif in their extracellular domain:
- Transforming growth factor a (TGF-a)
- EGF
- Neuregulins

Genetic interactions

Required for vein initiation and subsequent differentiation
Vn/EGFR signaling represses wing development
Misexpressing constitutive receptor, EGFRltop4.2, in the presumptive wing reduces the wing to a stump covered with sensilla characteristic of the proximal wing (hinge) region and expression of the wing specific gene vestigial was repressed (Wang, 2000)
4 ligans are known to modulate the function of DER
- Vein (vertebrate neuregulin isoform)
- Gurken (resemble TGF-a and are expressed as membrane-bound precursor molecules)
- Spitz (resemble TGF-a and are expressed as membrane-bound precursor molecules)
- Argos (novel inhibitory ligand)
Double in-situ hybridization reveals that the medial region of EGFR downregulation coincides with the region of kn gene expression (Fig. 5B). In kn mutants, downregulation of EGFR expression in the medial region is almost completely eliminated (Fig. 5C), indicating that the downregulation of EGFR expression is dependent on kn. Reciprocially, EGFR expression is greatly reduced in discs in which kn is ectopically expressed under the control of the MS1096-Gal4 driver (Fig. 5D). (Mohler, 2000)
vn is a target of EGFR signaling in the embryo (Golembo et al. 1999; Wessells et al. 1999)
Vn/EGFR signaling regulates Ap expression in a cell autonomous fashion only early in wing development
- ap expression partially overlaps that of vn in the second instar (Fig 4I) (Wang, 2000)
- ap can be induced ectopically in ventral clones misexpressing an activated form of the receptor, EGFR^lambdatop4.2 (Fig. 4J) (Wang, 2000)
- Egfr^tsla mutant clones generated in the first instar show autonomous loss of ap expression (Fig. 4K), whereas clones generated in the second instar express ap normally (data not shown) (Wang, 2000)
- loss of EGFR activity in whole discs from mid-first to mid-second instar (with a temperature-sensitive allele) results in complete loss of ap expression, whereas ap is still expressed in discs from larvae given a temperature shift slightly later during the second instar (Fig. 4L–N). (Wang, 2000)

Physical interactions

{Physical interactions}

Transcriptional Regulation

Patterned activation in the embryonic epidermis is primarily modulated by veinlet
Normally depressed in the 3-4 intervein region in the wing imaginal disc and is dependent on kn activity

Structure

{Structure}

Location (protein and transcript)

Activated in the epidermis of the late embryo
transcription is initially uniform throughout the wing blade, and by the end of the 3rd instar EGFR transcription is repressed along the wing margin and in a medial stripe across the wing blade region (Guichard, 1999)

Protein Modifications and Regulation

{Modifications}

Related to

In vertebrates, four different EGF receptor homologues constitute the ErbB superfamily

Mutations

Inactivating Vn/EGFR activity (with temp sensitive alleles; Egfr^ts1a, vn^tsWB240) during the second instar (a 24 hr period) caused loss of the notum (Fig. 1 E,F) (Wang, 2000). The wing developed but showed pattern abnormalities characteristic of vn hypomorphs (Fig 1E) (Wang, 2000). Later shifts during the third instar did not cause loss of the notum (data not shown) (Wang, 2000). This demonstrates Vn/EGFR activity is required for notum development in the second instar when wg is required to specify the wing (Ng, 1996).
In vn mutants, expression of Caup/Ara is lost (Fig. 2E) and loss of EGFR signaling, in EGFR^ts clones, in the medial notum resulted in a loss of Caup/Ara expression (Fig. 2G). However, clones in the lateral notum continued to express Caup/Ara (Fig. 2G), suggesting other factors regulate Iro-C gene expression in these cells at this stage (Wang, 2000)

Overexpression / Ectopic expression

ptc-GAL4 UAS-EGFR generates wings with fusion of veins 3 & 4 in the proximal portion of the wing (Fig 5E) (Mohler, 2000), which is similar to weak fu or kn mutations, suggesting that the downregulation oin EGFR in the medial wing may play a role in the spacing of veins 3 & 4 (Mohler, 2000). More distally the spacing of veins 3 & 4 appears normal. (Mohler, 2000)
EGFR driven by the MS1096 driver does not cause formation of ectopic vein between veins 3 & 4, although sgnificant amount of ectopic vein material is induced anterior to vein 3 and posterior to vein 4 (fig 5G) (Mohler, 2000) suggesting that the creation of a vein-free zone between veins 3 & 4 is not likelly to be explained solely by downregulation of EGFR by kn. (Mohler, 2000)
Ectopic expression of an activated form of the receptor, EGFR^lambdatop4.2 greatly reduced the size of the wing and partially transformed to hinge as evident from groups of ectopic sensilla characteristic of the proximal wing (hinge) and expression of vestigial was repressed cell autonomously (Fig. 2C & 3A-D). (Wang, 2000).

Reagents

{Reagents}