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• W1990256630 endingPage "4114" @default.
• W1990256630 startingPage "4110" @default.
• W1990256630 abstract "ErbB receptors, including the epidermal growth factor receptor (Egfr), are activated by EGF ligands to govern cell proliferation, survival, migration and differentiation. The different EGF-induced cell responses in development are regulated by deployment of multiple ligands. These inputs, however, engage only a limited number of intracellular pathways and are thought to elicit specific responses by regulating the amplitude or duration of the intracellular signal. The single Drosophila Egfr has four ligands: three of the TGF-α-type and a single neuregulin-like called vein (vn). Here, we used mutant combinations and gene replacement to determine the constraints of ligand specificity in development. Mutant analysis revealed extensive ligand redundancy in embryogenesis and wing development. Surprisingly, we found that the essential role of vn in development could be largely replaced by expression of any TGF-α ligand, including spitz (spi), in the endogenous vn pattern. vn mutants die as white undifferentiated pupae, but the rescued individuals showed global differentiation of adult body parts. Spi is more potent than Vn, and the best morphological rescue occurred when Spi expression was reduced to achieve an intracellular signaling level comparable to that produced by Vn. Our results show that the developmental repertoire of a strong ligand like Spi is flexible and at the appropriate level can emulate the activity of a weak ligand like Vn. These findings align with a model whereby cells respond similarly to an equivalent quantitative level of an intracellular signal generated by two distinct ligands regardless of ligand identity." @default.
• W1990256630 created "2016-06-24" @default.
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• W1990256630 creator A5058119070 @default.
• W1990256630 creator A5071257414 @default.
• W1990256630 date "2014-11-01" @default.
• W1990256630 modified "2023-09-27" @default.
• W1990256630 title "TGF-α ligands can substitute for the neuregulin Vein in<i>Drosophila</i>development" @default.
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• W1990256630 doi "https://doi.org/10.1242/dev.110171" @default.
• W1990256630 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25336739" @default.
• W1990256630 hasPublicationYear "2014" @default.
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