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

David Jukam, Baotong Xie, Jens Rister, David Terrell, Mark Charlton-Perkins, Daniela Pistillo, Brian Gebelein, Claude Desplan, Tiffany Cook

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number1238016
Issue number6155
StatePublished - 2013

ASJC Scopus subject areas

  • General


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