Transcriptional responses to hyperplastic MRL signalling in Drosophila.
Recent work has implicated the actin cytoskeleton in tissue size control and tumourigenesis, but how changes in actin dynamics contribute to hyperplastic growth is still unclear. Overexpression of Pico, the only Drosophila Mig-10/RIAM/Lamellipodin adapter protein family member, has been linked to tissue overgrowth via its effect on the myocardin-related transcription factor (Mrtf), an F-actin sensor capable of activating serum response factor (SRF). Transcriptional changes induced by acute Mrtf/SRF signalling have been largely linked to actin biosynthesis and cytoskeletal regulation. However, by RNA profiling, we find that the common response to chronic mrtf and pico overexpression in wing discs was upregulation of ribosome protein and mitochondrial genes, which are conserved targets for Mrtf/SRF and are known growth drivers. Consistent with their ability to induce a common transcriptional response and activate SRF signalling in vitro, we found that both pico and mrtf stimulate expression of an SRF-responsive reporter gene in wing discs. In a functional genetic screen, we also identified deterin, which encodes Drosophila Survivin, as a putative Mrtf/SRF target that is necessary for pico-mediated tissue overgrowth by suppressing proliferation-associated cell death. Taken together, our findings raise the possibility that distinct targets of Mrtf/SRF may be transcriptionally induced depending on the duration of upstream signalling.
Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Vincent
0000-0002-1925-6650
V
Jonchère
Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Nada
0000-0003-3607-2359
N
Alqadri
Centre for Computational Biology and Modelling (CCBM), Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
John
0000-0003-1657-356X
J
Herbert
Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Lauren
L
Dodgson
Centre for Cell Imaging, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
David
D
Mason
Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Giovanni
0000-0002-7597-4972
G
Messina
Centre for Computational Biology and Modelling (CCBM), Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Francesco
F
Falciani
Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK daimark.bennett@liverpool.ac.uk.|Centre for Cell Imaging, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Daimark
0000-0002-0014-2290
D
Bennett
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D030801:Animals, Genetically Modified; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006965:Hyperplasia / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012269:Ribosomal Proteins / Q000235:genetics; D015398:Signal Transduction; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D014921:Wings, Animal / Q000254:growth & development* / Q000378:metabolism
D000199:Actins; C412228:Det protein, Drosophila; D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; C488977:Mrtf protein, Drosophila; D009687:Nuclear Proteins; C533183:Pico protein, Drosophila; D012269:Ribosomal Proteins; D000077022:Survivin; D014157:Transcription Factors
Drosophila; MRL proteins; hyperplastic growth; serum response factor; wing development