Neuroglian activates Echinoid to antagonize the<i>Drosophila</i>EGF receptor signaling pathway

Rafique, Islam; Wei, Shu Yi; Chiu, Wei‐Yao; Hortsch, Michael; Hsu, Jui Chou

doi:10.1242/dev.00415

Cited by 60 publications

(84 citation statements)

References 29 publications

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“…Co-expression of ed and nrg in the eye exhibits a strong genetic synergy in inhibiting Egfr signaling and this effect requires the intracellular domain of Ed, but not that of Nrg. Together, these results suggest a model in which Ed functions as a receptor and is activated by either its own homophilic interaction or by an heterophilic ligand like Nrg (Islam et al, 2003).…”

Section: Introductionmentioning

confidence: 73%

“…Antibody staining was performed as described [Anti-Sc, anti-Sens and anti-β-galactosidase (Cubas et al, 1991); mAb22C10 (Hartenstein and Posakony, 1990); anti-ELAV (Islam et al, 2003); anti-N ICD (mAb9C6) (Parks et al, 2000)]. Polyclonal rabbit anti-Ed antibodies were generated against a synthetic peptide, corresponding to the Cterminal region of Ed (GEYSTTPNARNRRVIREIIV) and were used at a dilution of 1:200.…”

Section: Histochemistrymentioning

confidence: 99%

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Echinoid synergizes with the Notch signaling pathway inDrosophilamesothorax bristle patterning

et al. 2003

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in proneural clusters. Moreover, combinations of moderate loss-of-function conditions for ed and for different components of the N pathway show clear synergistic interactions manifested as strong neurogenic bristle phenotypes. We conclude that Ed is not essential for, but it facilitates, N signaling. It is known that the N and Egfr pathways act antagonistically in bristle development. Consistently, we find that Ed also antagonizes the bristlepromoting activity of the Egfr pathway, either by the enhancement of N signalling or, similar to the eye, by a more direct action on the Egfr pathway.

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Section: Introductionmentioning

confidence: 73%

Section: Histochemistrymentioning

confidence: 99%

Echinoid synergizes with the Notch signaling pathway inDrosophilamesothorax bristle patterning

et al. 2003

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“…The enhancing deficiencies Df(1)RA2 and Df(1)KA14 together define a region, 7F1;8A4, that includes Neuroglian (Nrg). In the developing eye, Nrg negatively regulates dEGFR activity (Islam et al 2003). Reducing Nrg gene dosage enhanced GMR-dRet activity, indicating that it also can negatively regulate dRet activity (Table 3).…”

Section: Men2bmentioning

confidence: 99%

A Drosophila Model of Multiple Endocrine Neoplasia Type 2

Read¹,

et al. 2005

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Dominant mutations in the Ret receptor tyrosine kinase lead to the familial cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Mammalian tissue culture studies suggest that Ret MEN2 mutations significantly alter Ret-signaling properties, but the precise mechanisms by which Ret MEN2 promotes tumorigenesis remain poorly understood. To determine the signal transduction pathways required for Ret MEN2 activity, we analyzed analogous mutations in the Drosophila Ret ortholog dRet. Overexpressed dRet MEN2 isoforms targeted to the developing retina led to aberrant cell proliferation, inappropriate cell fate specification, and excessive Ras pathway activation. Genetic analysis indicated that dRet MEN2 acts through the Ras-ERK, Src, and Jun kinase pathways. A genetic screen for mutations that dominantly suppress or enhance dRet MEN2 phenotypes identified new genes that are required for the phenotypic outcomes of dRet MEN2 activity. Finally, we identified human orthologs for many of these genes and examined their status in human tumors. Two of these loci showed loss of heterozygosity (LOH) within both sporadic and MEN2-associated pheochromocytomas, suggesting that they may contribute to Ret-dependent oncogenesis. D URING development, receptor tyrosine kinases (RTKs) integrate extracellular signals to influence cellular processes such as growth and differentiation. Signaling through RTKs requires ligand-induced oligomerization to direct tyrosine autophosphorylation; autophosphorylation both stimulates catalytic activity and creates phospho-tyrosine docking sites for cytoplasmic proteins that activate intracellular signaling pathways. To date, mutations in more than half of all RTKs have been implicated in human cancer (reviewed in Blume-Jensen and Hunter 2001). These mutations commonly function by relieving RTK regulatory constraints, leading to inappropriate kinase activity and hyperactivation of downstream pathways. These events promote oncogenic transformation by driving aberrant cellular growth, proliferation, and survival. Still, tumorigenesis requires mutations in multiple loci: along with dominant mutations in oncogenes such as RTKs, tumorigenesis also requires loss-of-function mutations in tumor suppressors. The relationship between oncogenic tyrosine kinases and tumor suppressors, and the extent to which mutations in each cooperate to direct oncogenic growth, is not well understood.The Ret RTK plays an essential role in both development and oncogenesis. During embryogenesis, Ret is required for development of the sympathetic and enteric nervous systems, the neural crest, and the excretory system (Schuchardt et al. 1994;Durbec et al. 1996;Enomoto et al. 2001). The extracellular portion of Ret contains cysteine repeats and a cadherinlike domain. The intracellular portion of Ret contains a tyrosine kinase catalytic domain and multiple tyrosine autophosphorylation sites. Four activating ligands have been identified: GDNF, Neurturin, Persephin, and Artemin all activate Ret through the GPI-linked co-

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“…Transient transfections were performed as in the procedure manual of the Calcium Phosphate Transfection Kit (Invitrogen). Cell aggregation assays were performed as described (Islam et al, 2003).…”

Section: Cell Culturementioning

confidence: 99%

Glial cell adhesive molecule unzipped mediates axon guidance in Drosophila

Ding

Wang

Luo

et al. 2010

Developmental Dynamics

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Axon guidance needs help from the glial cell system during embryogenesis. In the Drosophila embryonic central nervous system (CNS), longitudinal glia (LG) have been implicated in axon guidance but the mechanism remains unclear. We identified the protein encoded by the Drosophila gene unzipped (uzip) as a novel cell adhesion molecule (CAM). Uzip expressed in Drosophila S2 cells triggered cell aggregation through homophilic binding. In the embryonic CNS, Uzip was mainly produced by the LG but was also located at axons, which is consistent with the secretion of Uzip expressed in cultured cells. Although uzip mutants displayed no axonal defect, loss of uzip enhanced the axonal defects in the mutant of N‐cadherin (CadN) and the Wnt gene family member wnt5. Overexpression of uzip could rescue the phenotype in the CadNuzipD43 mutant. Thus, Uzip is a novel CAM from the LG regulating axon guidance. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.

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Neuroglian activates Echinoid to antagonize theDrosophilaEGF receptor signaling pathway

Cited by 60 publications

References 29 publications

Echinoid synergizes with the Notch signaling pathway inDrosophilamesothorax bristle patterning

Echinoid synergizes with the Notch signaling pathway inDrosophilamesothorax bristle patterning

A Drosophila Model of Multiple Endocrine Neoplasia Type 2

Glial cell adhesive molecule unzipped mediates axon guidance in Drosophila

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