Ras1 Promotes Cellular Growth in the Drosophila Wing

Abstract

The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation. To understand how Ras regulates proliferation in vivo, we activated or inactivated Ras in cell clones in the developing Drosophila wing. Cells lacking Ras were smaller, had reduced growth rates, accumulated in G1, and underwent apoptosis due to cell competition. Conversely, activation of Ras increased cell size and growth rates and promoted G1/S transitions. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit.

Molecular mechanism of size control in development and human diseases

“…Cells lacking ras were smaller and had reduced growth rates. Conversely, overexpressing Ras (dRasV12) in clones of proliferating cells resulted in similar phenotypes as those after overexpressing dMyc [135]. Consistently, expression of in rapidly proliferating tissues.…”

“…Therefore, it is still possible that www.cell-research.com | Cell Research Xiaolong Yang and Tian Xu 721 npg activated Ras in mouse heart tissue also increases heart size as a result of cell enlargement [136]. Ras activates cell growth by either activating dMyc post-transcriptionally or activating PI3K (Figure 3; [135,137,138]). In addition, Ras may also regulate cell growth by activating Rac, another GTPase [139].…”

“…Recently, a direct role for Ras in controlling cellular growth was found in Drosophila [135]. Cells lacking ras were smaller and had reduced growth rates.…”

The BTB/POZ-ZF Transcription Factor dPLZF Is Involved in Ras/ERK Signaling During Drosophila Wing Development

“…Therefore, Ras/ERK activation in a specific row of cells determines the fate of the cells as future wing veins. Consistent with this observation, loss-of-function mutations of the Ras/ERK pathway components result in loss of veins, whereas gain-offunction alleles and/or overexpression of these components induce ectopic vein development (Brunner et al, 1994;Kim et al, 2006;Prober and Edgar, 2000;Sturtevant and Bier, 1995). Additionally, phosphorylated cytoplasmic ERK promotes vein differentiation in the developing wing vein and margin cells during the larval and early pupal stage (Marenda et al, 2006).…”

Myc in model organisms: A view from the flyroom

“…Overexpression of dMyc in these cells increases Cyclin E levels and accelerates the G1/S transition [19,27]. Cyclin E mRNA levels are moderately enhanced in response to dMyc expression, but Cyclin E protein is increased disproportionately, suggesting that most of the increase is due to post-transcriptional regulation [27,28]. This post-transcriptional regulation could be mediated by signaling from the small GTPase, Ras, as it is in mammals, since in ras mutant cells dMyc expression no longer induces high Cyclin E levels [27].…”