| RRC ID |
32500
|
| Author |
Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T.
|
| Title |
Opposite feedbacks in the Hippo pathway for growth control and neural fate.
|
| Journal |
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.
|
| Volume |
342(6155)
|
| Pages |
1238016
|
| Published |
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
|
| Times Cited |
48
|
| Resource |
| Drosophila |
12399R-2 |
