Abstract
Signaling pathways are reused for multiple purposes in plant and animal development. The Hippo pathway in mammals and Drosophila coordinates proliferation and apoptosis via the coactivator and oncoprotein YAP/Yorkie (Yki), which is homeostatically regulated through negative feedback. In the Drosophila eye, cross-repression between the Hippo pathway kinase LATS/Warts (Wts) and growth regulator Melted generates mutually exclusive photoreceptor subtypes. Here, we show that this all-or-nothing neuronal differentiation results from Hippo pathway positive feedback: Yki both represses its negative regulator, warts, and promotes its positive regulator, melted. This postmitotic Hippo network behavior relies on a tissue-restricted transcription factor network-including a conserved Otx/Orthodenticle-Nrl/Traffic Jam feedforward module-that allows Warts-Yki-Melted to operate as a bistable switch. Altering feedback architecture provides an efficient mechanism to co-opt conserved signaling networks for diverse purposes in development and evolution.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / cytology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / growth & development*
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Feedback, Physiological
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Gene Expression Regulation, Developmental*
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Gene Regulatory Networks
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Homeodomain Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mitosis
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Neurogenesis / genetics*
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Nuclear Proteins / metabolism*
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Photoreceptor Cells, Invertebrate / cytology
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Photoreceptor Cells, Invertebrate / metabolism
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Photoreceptor Cells, Invertebrate / physiology*
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Protein Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Signal Transduction*
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Trans-Activators / metabolism*
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YAP-Signaling Proteins
Substances
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Drosophila Proteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Trans-Activators
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YAP-Signaling Proteins
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Yki protein, Drosophila
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melt protein, Drosophila
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oc protein, Drosophila
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Protein Kinases
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wts protein, Drosophila
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Protein Serine-Threonine Kinases
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hpo protein, Drosophila