Transcriptional responses to hyperplastic MRL signalling inDrosophila

Abstract

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.

Activation of the actin/MRTF-A/SRF signalling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation

“…These observations are consistent with a role for P-cad in potentiating the DMRTF/DSRF signalling pathway. Accordingly, knocking down MESK2 (MESK2-IR) or deterin ( det -IR), two DMRTF/DSRF target genes [23], restored the growth and circularity of P-cad-expressing wings (Supp. Fig.…”

The True Story of Yeti, the “Abominable” Heterochromatic Gene of Drosophila melanogaster

“…Finally, YETI protein has also been implicated in cell cycle control in both mitosis and meiosis (Billmann et al, 2016). According with these results, it has been reported that Myc, a well-known oncogenic player (Bellosta et al, 2005; Jonchere et al, 2017; Taylor et al, 2017), and the DOMINO ATPase interact each other and are required for normal asymmetric neuroblast (NB) division. Live-imaging analysis of dom -or myc -depleted NBs showed that spindle morphology is affected resulting in aberrant divisions (Rust et al, 2018).…”

droTAG: Adapting dTAG Toolkit to Drosophila Melanogaster

“…In conclusion, drawing up droTAG could be indispensable for all the worldwide fly researchers, including us, who have the possibility to highlight phenotypes that otherwise they cannot see by using conventional RNA interference approaches [10][11][12][13][14].…”