RRC ID 32500
著者 Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T.
タイトル Opposite feedbacks in the Hippo pathway for growth control and neural fate.
ジャーナル Science
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.
巻・号 342(6155)
ページ 1238016
公開日 2013-10-11
DOI 10.1126/science.1238016
PII science.1238016
PMID 23989952
PMC PMC3796000
MeSH Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Feedback, Physiological Gene Expression Regulation, Developmental* Gene Regulatory Networks Homeodomain Proteins / metabolism Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Mitosis Neurogenesis / genetics* Nuclear Proteins / metabolism* Photoreceptor Cells, Invertebrate / cytology Photoreceptor Cells, Invertebrate / metabolism Photoreceptor Cells, Invertebrate / physiology* Protein Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Signal Transduction* Trans-Activators / metabolism* YAP-Signaling Proteins
IF 41.846
引用数 48
リソース情報
ショウジョウバエ 12399R-2