TY - JOUR
T1 - Opposite feedbacks in the Hippo pathway for growth control and neural fate
AU - Jukam, David
AU - Xie, Baotong
AU - Rister, Jens
AU - Terrell, David
AU - Charlton-Perkins, Mark
AU - Pistillo, Daniela
AU - Gebelein, Brian
AU - Desplan, Claude
AU - Cook, Tiffany
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1238016
DO - 10.1126/science.1238016
M3 - Article
C2 - 23989952
AN - SCOPUS:84883124586
SN - 0036-8075
VL - 342
JO - Science
JF - Science
IS - 6155
M1 - 1238016
ER -