Control of Compartment Size by an EGF Ligand from Neighboring Cells

Abstract

Insect bodies are subdivided into anterior (A) and posterior (P) compartments: cohesive fields of distinct cell lineage and cell affinity . Like organs in many animal species, compartments can develop to normal sizes despite considerable variation in cell division . This implies that overall compartment dimensions are subject to genetic control, but the mechanisms are unknown. Here, studying Drosophila's embryonic segments, I show that P compartment dimensions depend on epidermal growth factor receptor (EGFR) signaling. I suggest the primary activating ligand is Spitz, emanating from neighboring A compartment cells. Spi/EGFR activity stimulates P compartment cell enlargement and survival, but evidence is presented that Spitz is secreted in limited amounts, so that increasing the number of cells within the P compartment causes the per-cell Spitz level to drop. This leads to compensatory apoptosis and cell-size reductions that preserve compartment dimensions. Conversely, I propose that lowering P compartment cell numbers enhances per-cell Spitz availability; this increases cell survival and cell size, again safeguarding compartment size. The results argue that the gauging of P compartment size is due, at least in part, to cells surviving and growing according to Spi availability. These data offer mechanistic insight into how diffusible molecules control organ size.

EGFR-dependent network interactions that pattern Drosophila eggshell appendages

“…Some of the most advanced studies of EGFR signaling have been carried out in Drosophila, which, similar to other organisms, uses its EGFR pathway throughout development (Shilo, 2003). Drosophila EGFR signaling is involved in patterning of essentially all tissue types and compartments in the embryo (Golembo et al, 1996;Szuts et al, 1998;Yagi et al, 1998;Parker, 2006). In larval and pupal stages, EGFR controls growth, patterning and morphogenesis of multiple organs and structures, including wing veins and photoreceptor arrays (de Celis, 2003;Roignant and Treisman, 2009).…”

Drosophila-based in vivo assay for the validation of inhibitors of the epidermal growth factor receptor/Ras pathway

“…In the eye, EGFR plays multiple roles (Kumar et al 1998), which include control of cell proliferation, neuronal differentiation in the posterior margin of the imaginal disc (Xu and Rubin 1993), cell recruitment (Baker and Rubin 1989), cluster/founder cell spacing (Baker and Rubin 1992;Herberlein and Moses 1995), spacing of the R8 cells, cell survival and later recruitment of non-R8 cells. Once the pre-cluster is recruited, a wave of a second mitotic cycle sweeps across the imaginal disc of the eye posterior to the furrow that is governed by EGFR signalling (Parker 2006). Besides, EGFR has a specifi c role in controlling the size of most of the epidermal cells (Wang et al 2000).…”

Scaling of cytoskeletal organization with cell size inDrosophila

“…These were the haploid progeny of ms(3)k81 males, which undergo an extra cell division in early embryogenesis, and embryos that overexpress Cyclin E, which have an extra division in midembryogenesis (Yasuda et al. , 1995; Parker, 2006). The average cell length in ms(3)k81 and Cyclin E-overexpressing (CycE-OE) embryos was reduced by 35 and 28%, respectively (Figure 3, A and C, and Supplemental Table S1).…”