Opposite Feedbacks in the Hippo Pathway for Growth Control and Neural Fate

• Published in: Science (American Association for the Advancement of Science) 2013-10, Vol.342 (6155), p.211-211
• Main Authors: Jukam, David, Xie, Baotong, Rister, Jens, Terrell, David, Charlton-Perkins, Mark, Pistillo, Daniela, Gebelein, Brian, Desplan, Claude, Cook, Tiffany
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell growth; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Fate; Feedback, Physiological; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Homeodomain Proteins - metabolism; Individualized Instruction; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mitosis; Negative feedback; Networks; Neurogenesis - genetics; Neurons; Nuclear Proteins - metabolism; Photoreceptor Cells, Invertebrate - cytology; Photoreceptor Cells, Invertebrate - metabolism; Photoreceptor Cells, Invertebrate - physiology; Photoreceptors; Protein Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; RESEARCH ARTICLE SUMMARY; Signal Transduction; Trans-Activators - metabolism; Transcription factors; Vertebrates: nervous system and sense organs; Warts
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1238016

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.