TitleMultiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in Drosophila tracheoblasts.
Publication TypeJournal Article
Year of Publication2020
AuthorsKizhedathu A, Kunnappallil RSebastian, Bagul AV, Verma P, Guha A
JournalElife
Volume9
Date Published2020 Sep 02
ISSN2050-084X
Abstract

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.

DOI10.7554/eLife.57056
Alternate JournalElife
PubMed ID32876044
Grant ListinStem Core Grant / / Department of Biotechnology , Ministry of Science and Technology /
InStem Core Grant / / Department of Biotechnology , Ministry of Science and Technology /