Specification of Differentiated Adult Progenitors via Inhibition of Endocycle Entry in the Drosophila Trachea

Abstract

A population of Drosophila adult tracheal progenitor cells arises from differentiated cells of the larval main trachea that retain the ability to reenter the cell cycle and give rise to the multiple adult tracheal cell types. These progenitors are unique to the second tracheal metamere as homologous cells from other segments, express fizzy-related (fzr), the Drosophila homolog of CDH1 protein of the APC complex, and enter endocycle and do not contribute to adult trachea. Here, we examine the mechanisms for their quiescence and show that they reenter the cell cycle by expression of string/cdc25 through ecdysone. Furthermore, we show that preventing endocycle entry is both necessary and sufficient for these tracheal cells to exhibit markers of adult progenitors, thus modifying their genetic program. Finally, we show that Hox-mediated regulation of fzr expression is responsible for progenitor identity and thus specifies a group of differentiated cells with facultative stem cell features.

Drosophila Lung Cancer Models Identify Trametinib plus Statin as Candidate Therapeutic

“…3L,M). During metamorphosis, most larval tissue including the tracheal epithelium histolyze and are replaced by imaginal tissue (Djabrayan et al 2014; Cabernard and Affolter 2005; Sato and Kornberg 2002). These GFP-positive abdominal tumor-like foci likely derive from regions that failed to histolyze properly (Fig.…”

A cellular process that includes asymmetric cytokinesis remodels the dorsal tracheal branches in Drosophila larvae

“…Alone among tracheal metameres, remodeling in Tr2 also includes the DT and VB. The special identity of Tr2, where the ASP originates (Sato and Kornberg, 2002), is specified by a Hox code (Sato et al, 2008;Djabrayan et al, 2014). It is interesting that the cells in the DB of Tr2 divide a few hours earlier than those from the other anterior tracheomeres and generally have thicker branches by the WL stage (Fig.…”

“…the entire Tr2 (where the ASP originates), the dorsal branches (DBs) of Tr3-Tr5 and all the spiracular branches (SBs), were found to retain their proliferative potential (Guha and Kornberg, 2005;Guha et al, 2008;Sato et al, 2008;Weaver and Krasnow, 2008;Pitsouli and Perrimon, 2010). Although some populations of polyploid cells have been shown to re-enter the mitotic cycle (Fox et al, 2010), the cells that the DBs and SBs comprise are likely diploid cells, and functionally similar to those in the imaginal disks (Sato et al, 2008;Weaver and Krasnow, 2008;Djabrayan et al, 2014).…”

Ecdysone signaling induces two phases of cell cycle exit inDrosophilacells

“…A pulse of ecdysone signaling occurs during the initiation of metamorphosis at the larva-to-puparium transition (Ashburner, 1989), where extensive changes in proliferation, cell shape, apoptosis and cell adhesion take place. For example, the strong ecdysone pulse at the larva-to-puparium transition leads to activation of apoptotic programs in many larval cell types such as the salivary gland, muscle and midgut (Jiang et al, 1997, 2000; Lee et al, 2002; Yin and Thummel, 2004; Zirin et al, 2013) while in other tissues such as the abdominal histoblasts or dorsal adult progenitor (DAP) cells of trachea, proliferation of adult progenitors is triggered (Djabrayan et al, 2014; Ninov et al, 2009). In the case of abdominal histoblasts, these cells remain quiescent in the G2 phase of the cell cycle during larval development, and are poised to enter mitosis and proliferate when the rate-limiting G2-M cdc25c phosphatase String (Stg) is induced by ecdysone.…”