Drosophila myc Regulates Cellular Growth during Development

Abstract

Transcription factors of the Myc proto-oncogene family promote cell division, but how they do this is poorly understood. Here we address the functions of Drosophila Myc (dMyc) during development. Using mosaic analysis in the fly wing, we show that loss of dMyc retards cellular growth (accumulation of cell mass) and reduces cell size, whereas dMyc overproduction increases growth rates and cell size. dMyc-induced growth promotes G1/S progression but fails to accelerate cell division because G2/M progression is independently controlled by Cdc25/String. We also show that the secreted signal Wingless patterns growth in the wing primordium by modulating dMyc expression. Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism.

The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo

“…The coexpressed GFP allowed for the identification of the clones; since larval wing discs consist essentially of a monolayer of undifferentiated cells, the areas of such clones provide a good measure for their volume increase. Consistent with published observations (Johnston et al, 1999), MycWT overexpression strongly promotes clonal growth (Fig. 4A, B), and so does MycMB2A.…”

“…5C, compare "-" and "ΔN"), thus demonstrating its activity both during the earlier proliferative and the later differentiation phase. Note that we would not expect any Myc mutant to increase the number of ommatidia in dm + eyes, since Myc overexpression does not increase cell division rates in wild type cells (Johnston et al, 1999). Instead, expression of the other Myc forms slightly or significantly reduces the number of ommatidia in this assay, reflecting the proapoptotic activity of these proteins .…”

“…dm P0 ) are delayed in their development and eclose as small adults (Johnston et al, 1999), whereas dm 4 mutant flies (null for Myc) fail to grow as larvae and die within a few days of hatching (Pierce et al, 2004;Pierce et al, 2008;Steiger et al, 2008). Conversely, overexpression of Myc promotes cellular growth (Johnston et al, 1999), endoreplication (Maines et al, 2004;Pierce et al, 2004), and apoptosis (De La Cova et al, 2004;Montero et al, 2008). In the present study, we expressed wild type and mutant forms of Myc (carrying mutations in MB2, MB3, or the N-terminus) in vivo.…”

“…Source of additional flies: GAL4 drivers (Drosophila stock center at Bloomington), act-FRT-CD2-FRT-GAL4 (Neufeld et al, 1998), GMR-FRT-w + -FRT-GAL4 (Brogiolo et al, 2001), tub-FRT-Myc-FRT-GAL4 (De La Cova et al, 2004, dm P0 (Johnston et al, 1999), dm 2 (Maines et al, 2004), dm 4 (Pierce et al, 2004), dm 4 mnt 1 (Pierce et al, 2008), dm PL35 & dm PG45 (Benassayag et al, 2005).…”

A role for Myc in facilitating transcription activation by E2F1

“…In particular, genetic studies would suggest that Myc is not required for cell-cycle transition, but rather for the regulated growth of cells as they enter a proliferative state (Johnston et al, 1999). Such a role would be consistent with the nature of genes apparently regulated by Myc which include not only genes such as the E2Fs that are critical for generating the DNA replication machinery, but also a variety of genes encoding basic metabolic activities essential for growing cells.…”