Coordination of Growth and Cell Division in the Drosophila Wing

Abstract

In most tissues, cell division is coordinated with increases in mass (i.e., growth). To understand this coordination, we altered rates of division in cell clones or compartments of the Drosophila wing and measured the effects on growth. Constitutive overproduction of the transcriptional regulator dE2F increased expression of the S- and M-phase initiators Cyclin E and String (Cdc25), thereby accelerating cell proliferation. Loss of dE2F or overproduction of its corepressor, RBF, retarded cell proliferation. These manipulations altered cell numbers over a 4- to 5-fold range but had little effect on clone or compartment sizes. Instead, changes in cell division rates were offset by changes in cell size. We infer that dE2F and RBF function specifically in cell cycle control, and that cell cycle acceleration is insufficient to stimulate growth. Variations in dE2F activity could be used to coordinate cell division with growth.

The conserved PI3′K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila

“…We dissociated wing imaginal disc cells from wild-type and Dakt1 mutant larvae, stained the cells with the DNA dye Hoechst and examined them using¯ow cytometry. This method allows us to determine the relative size of a population of cells by forward scatter (FSC) distribution (Neufeld et al, 1998). Dissociated To examine the role of Dakt1 in the development of the eye, we utilized the eyeless promoter to make Dakt1 homozygous mutant eyes ( Figure 6b).…”

“…The 0.025 mm 2 area was then divided by the average number of hairs in the designated area. The total number of dorsal wing blade inter-vein cells for the sample of wings was calculated by multiplying the average number of hairs in a 0.025 mm 2 rectangle by total average area of the dorsal wing blade from the eight wing samples divided by 0.025 mm 2 (Montagne et al, 1999;Neufeld et al, 1998).…”

The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function 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).…”

Retinoblastoma family genes

“…For example, overexpression of dE2F1 in the Drosophila developing wing accelerates both G1/S and G2/M transitions, while overexpression of RBF slowed all phase of the cell cycle, with the greatest effect on S-phase duration (Neufeld et al, 1998). These cell cycle effects are likely due to the ability of RBF and dE2F1 to control the expression of targets such as cyclin E and string (Drosophila cdc25), as well as multiple DNA replication factors that regulate the progression of different cell cycle phases.…”