Nonautonomous Apoptosis Is Triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila

Abstract

Tissue remodeling involves collective cell movement, and cell proliferation and apoptosis are observed in both development and disease. Apoptosis and proliferation are considered to be closely correlated, but little is known about their coordinated regulation in physiological tissue remodeling in vivo. The replacement of larval abdominal epidermis with adult epithelium in Drosophila pupae is a simple model of tissue remodeling. During this process, larval epidermal cells (LECs) undergo apoptosis and are replaced by histoblasts, which are adult precursor cells. By analyzing caspase activation at the single-cell level in living pupae, we found that caspase activation in LECs is induced at the LEC/histoblast boundary, which expands as the LECs die. Manipulating histoblast proliferation at the LEC/histoblast boundary, either genetically or by UV illumination, indicated that local interactions with proliferating histoblasts triggered caspase activation in the boundary LECs. Finally, by monitoring the spatiotemporal dynamics of the S/G 2 /M phase in histoblasts in vivo, we found that the transition from S/G 2 phases is necessary to induce nonautonomous LEC apoptosis at the LEC/histoblast boundary. The replacement boundary, formed as caspase activation is regulated locally by cell-cell communication, may drive the dynamic orchestration of cell replacement during tissue remodeling.

Mitochondrial defects trigger proliferation of neighbouring cells via a senescence-associated secretory phenotype in Drosophila

“…Cells undergoing cellular senescence exhibit an irreversible cell cycle arrest in G1 phase, which is one of the critical cellular events in cellular senescence. We thus examined whether clones of Ras-activated cells cause cell cycle arrest in G1 phase in imaginal disc using the cell cycle monitoring probe S/G2/M-Green 25,26 .…”

Apoptotic and Nonapoptotic Caspase Functions in Animal Development

“…This replacement boundary, formed as caspase activation is regulated locally by cell-cell communication, may drive the dynamic orchestration of cell replacement during tissue remodeling by competitive interaction (Fig. 4) (Nakajima et al 2011). …”

The peripheral nervous system supports blood cell homing and survival in theDrosophilalarva

“…UAS-S/G2/M-Green (Nakajima et al, 2010) shows fluorescence during the S/G2/M phases of the cell cycle, and absence of fluorescence during G1, corresponding to cell cycle quiescence (Fig. 4C).…”

“…ato 1 (Jarman et al, 1993) homozygotes were identified by absence of TM3 Kr-GAL4, UAS-GFP. UAS/GAL4 system (Brand and Perrimon, 1993) and other lines used were 2-38-GAL4 (Rothenfluh et al, 2006;Corl et al, 2009), elav-GAL4 (Lin and Goodman, 1994), 21-7-GAL4 (Song et al, 2007), repo-GAL4 (Sepp et al, 2001), gliotactin-GAL4 (Sepp and Auld, 1999), en-GAL4 (FlyBase), He-GAL4 (Zettervall et al, 2004), Hml-GAL4 (Sinenko and MatheyPrevot, 2004), Pxn-GAL4 (Stramer et al, 2005), srpHemo-GAL4 (Brückner et al, 2004), Sal-GAL4 (Thomas et al, 1995), UAS-S/G2/M-Green fucci (Sakaue-Sawano et al, 2008;Nakajima et al, 2010), UAS-EGFP (Halfon et al, 2002), UAS-mCD8 GFP (Lee and Luo, 1999), UAS-Stinger (Barolo et al, 2004) (Mlodzik et al, 1990). GAL4 drivers were recombined with UAS-EGFP to visualize expression patterns.…”