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

68 Scopus citations


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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