Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila
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...
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| Format: | Article |
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eLife Sciences Publications Ltd
2018-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/29988 |
| _version_ | 1811181095004143616 |
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| author | Amrutha Kizhedathu Archit V Bagul Arjun Guha |
| author_facet | Amrutha Kizhedathu Archit V Bagul Arjun Guha |
| author_sort | Amrutha Kizhedathu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:12:41Z |
| format | Article |
| id | doaj.art-777d6731a382485ebe72c904c2fbe6e2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:41Z |
| publishDate | 2018-04-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-777d6731a382485ebe72c904c2fbe6e22022-12-22T04:32:26ZengeLife Sciences Publications LtdeLife2050-084X2018-04-01710.7554/eLife.29988Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in DrosophilaAmrutha Kizhedathu0Archit V Bagul1Arjun Guha2https://orcid.org/0000-0002-3753-1484Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India; SASTRA University, Thanjavur, IndiaInstitute for Stem Cell Biology and Regenerative Medicine, Bangalore, IndiaInstitute for Stem Cell Biology and Regenerative Medicine, Bangalore, IndiaImaginal 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.https://elifesciences.org/articles/29988TracheoblastsG2 arrestATR/mei-41Chk1/Grapescellular growthhypertrophic growth |
| spellingShingle | Amrutha Kizhedathu Archit V Bagul Arjun Guha Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila eLife Tracheoblasts G2 arrest ATR/mei-41 Chk1/Grapes cellular growth hypertrophic growth |
| title | Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila |
| title_full | Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila |
| title_fullStr | Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila |
| title_full_unstemmed | Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila |
| title_short | Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila |
| title_sort | negative regulation of g2 m by atr mei 41 chk1 grapes facilitates tracheoblast growth and tracheal hypertrophy in drosophila |
| topic | Tracheoblasts G2 arrest ATR/mei-41 Chk1/Grapes cellular growth hypertrophic growth |
| url | https://elifesciences.org/articles/29988 |
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