Larval tracheae of Drosophila harbor progenitors of the adult tracheal system (tracheoblasts). We showed previously that thoracic tracheoblasts arrest in the G2 phase of the cell cycle in an ATR-Checkpoint Kinase1(Chk1)-dependent manner prior to division and morphogenesis (Kizhedathu et al., 2018). Here we investigate developmental regulation of Chk1 activation. We report that Wnt signaling is high in tracheoblasts and is necessary for high levels of activated (phosphorylated) Chk1. We find that canonical Wnt signaling facilitates this by transcriptional upregulation of Chk1 in cells that have ATR kinase activity. Wnt signalling is dependent on four Wnts (Wg, Wnt5, 6,10) that are expressed at high levels in arrested tracheoblasts and downregulated at mitotic re-entry. Interestingly, none of the Wnts are dispensable and act synergistically to induce Chk1. Finally, we show that downregulation of Wnt signalling and Chk1 expression leads to mitotic re-entry and the concomitant upregulation of Dpp signalling, driving tracheoblast proliferation.
All data generated or analysed during this study are included in the manuscript.
- Arjun Guha
- Arjun Guha
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Amin S. Ghabrial, Columbia University, United States
© 2020, Kizhedathu et al.
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