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PMID: 23989952 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Opposite feedbacks in the Hippo pathway for growth control and neural fate.

Science (New York, N.Y.) ·Vol. 342 ·No. 6155 ·2013-10-11 ·Pages 1238016

Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T

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.

MeSH Terms
Animals Drosophila Proteins/genetics,metabolism Drosophila melanogaster/cytology,genetics,growth & development Feedback, Physiological Gene Expression Regulation, Developmental Gene Regulatory Networks Homeodomain Proteins/metabolism Intracellular Signaling Peptides and Proteins/genetics,metabolism Mitosis Neurogenesis/genetics Nuclear Proteins/metabolism Photoreceptor Cells, Invertebrate/cytology,metabolism,physiology Protein Kinases/genetics Protein Serine-Threonine Kinases/metabolism Signal Transduction Trans-Activators/metabolism YAP-Signaling Proteins
Chemicals
Drosophila Proteins Homeodomain Proteins Intracellular Signaling Peptides and Proteins Nuclear Proteins Trans-Activators YAP-Signaling Proteins Yki protein, Drosophila melt protein, Drosophila oc protein, Drosophila Protein Kinases wts protein, Drosophila Protein Serine-Threonine Kinases hpo protein, Drosophila
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jukam David
Center for Developmental Genetics, Department of Biology, New York University, New York, NY 10003, USA.
Xie Baotong
Rister Jens
Terrell David
Charlton-Perkins Mark
Pistillo Daniela
Gebelein Brian
Desplan Claude
Cook Tiffany
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1238016
Published
2013-10-11
Epub
2013-00-29
Pages
1238016
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3796000
Subset
IM
Grants
NEI NIH HHS · R01 EY013012 · United States
NEI NIH HHS · R01 EY13012 · United States
External Links
PubMed source DOI: 10.1126/science.1238016 PMC Full Text View journal details
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