Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in Drosophila tracheoblasts
Larval tracheae of Drosophila harbour progenitors of the adult tracheal system (tracheoblasts). Thoracic tracheoblasts are arrested in the G2 phase of the cell cycle in an ATR (mei-41)-Checkpoint Kinase1 (grapes, Chk1) dependent manner prior to mitotic re-entry. Here we investigate developmental regulation of Chk1 activation. We report that Wnt signaling is high in tracheoblasts and this is necessary for high levels of activated (phosphorylated) Chk1. We find that canonical Wnt signaling facilitates this by transcriptional upregulation of Chk1 expression 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 are 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.
Article and author information
Department of Biotechnology , Ministry of Science and Technology (inStem Core Grant)
- Arjun Guha
Department of Biotechnology , Ministry of Science and Technology (InStem Core Grant)
- 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
- Received: March 20, 2020
- Accepted: August 29, 2020
- Accepted Manuscript published: September 2, 2020 (version 1)
- Accepted Manuscript updated: September 9, 2020 (version 2)
- Version of Record published: September 21, 2020 (version 3)
- Version of Record updated: September 24, 2020 (version 4)
© 2020, Kizhedathu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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