Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in Drosophila tracheoblasts

Elife. 2020 Sep 2:9:e57056. doi: 10.7554/eLife.57056.

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 signaling 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 signaling and Chk1 expression leads to mitotic re-entry and the concomitant upregulation of Dpp signaling, driving tracheoblast proliferation.

Keywords: Checkpoint Kinase I; D. melanogaster; G2 arrest; Wnt; cell biology; developmental biology; tracheoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Checkpoint Kinase 1* / genetics
  • Checkpoint Kinase 1* / metabolism
  • Drosophila / cytology
  • Drosophila / embryology
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • G2 Phase / genetics*
  • Trachea* / cytology
  • Trachea* / embryology
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics*

Substances

  • Drosophila Proteins
  • Wnt Proteins
  • dpp protein, Drosophila
  • Checkpoint Kinase 1
  • grp protein, Drosophila