TitleNegative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila.
Publication TypeJournal Article
Year of Publication2018
AuthorsKizhedathu A, Bagul AV, Guha A
Date Published2018 Apr 16

Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages and proliferate thereafter. Here we investigate the mechanism and implications of G2 arrest in progenitors of the adult thoracic tracheal epithelium (tracheoblasts). We report that tracheoblasts pause in G2 for ~48-56 h and grow in size over this period. Surprisingly, tracheoblasts arrested in G2 express drivers of G2-M like Cdc25/String (Stg). We find that mechanisms that prevent G2-M are also in place in this interval. Tracheoblasts activate Checkpoint Kinase 1/Grapes (Chk1/Grp) in an ATR/mei-41-dependent manner. Loss of ATR/Chk1 led to precocious mitotic entry ~24-32 h earlier. These divisions were apparently normal as there was no evidence of increased DNA damage or cell death. However, induction of precocious mitoses impaired growth of tracheoblasts and the tracheae they comprise. We propose that ATR/Chk1 negatively regulate G2-M in developing tracheoblasts and that G2 arrest facilitates cellular and hypertrophic organ growth.

Alternate JournalElife
PubMed ID29658881
PubMed Central IDPMC5953539
Grant ListinStem Core Funds / / Department of Biotechnology, Ministry of Science and Technology /
Ramalingaswamy Fellowship, inStem/DBT/8241 / / Ministry of Science and Technology /
inStem Core Funds / / Department of Biotechnology , Ministry of Science and Technology /
inStem/DBT/8241 / / Ramalingaswamy Fellowship, Department of Biotechnology , Ministry of Science and Technology /