Publication Date:
2013-08-31
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796000/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jukam, David -- Xie, Baotong -- Rister, Jens -- Terrell, David -- Charlton-Perkins, Mark -- Pistillo, Daniela -- Gebelein, Brian -- Desplan, Claude -- Cook, Tiffany -- R01 EY013012/EY/NEI NIH HHS/ -- R01 EY13012/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):1238016. doi: 10.1126/science.1238016. Epub 2013 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Developmental Genetics, Department of Biology, New York University, New York, NY 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23989952" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Drosophila Proteins/genetics/*metabolism
;
Drosophila melanogaster/cytology/genetics/*growth & development
;
Feedback, Physiological
;
*Gene Expression Regulation, Developmental
;
Gene Regulatory Networks
;
Homeodomain Proteins/metabolism
;
Intracellular Signaling Peptides and Proteins/genetics/*metabolism
;
Mitosis
;
Neurogenesis/*genetics
;
Nuclear Proteins/*metabolism
;
Photoreceptor Cells, Invertebrate/cytology/metabolism/*physiology
;
Protein Kinases/genetics
;
Protein-Serine-Threonine Kinases/*metabolism
;
*Signal Transduction
;
Trans-Activators/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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