@article{8ac519589cd14c639285d24b24f05fd3,
title = "ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit",
abstract = "During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.",
keywords = "Drosophila, cell division, development, extracellular matrix, growth control, mechanics, quantitative biology, simulations, Epidermis, Animals, Cell Cycle, Cell Division, Epidermal Cells, Mice",
author = "Davis, {John Robert} and Ainslie, {Anna P.} and Williamson, {John J.} and Ana Ferreira and Alejandro Torres-S{\'a}nchez and Andreas Hoppe and Federica Mangione and Smith, {Matthew B.} and Enrique Martin-Blanco and Guillaume Salbreux and Nicolas Tapon",
note = "Funding Information: We thank Y. Bella{\"i}che, D. Bohmann, B. Stramer, K. Irvine, M. Uhlirova, and the Bloomington Drosophila Stock Centre for fly stocks. We are grateful to M. Renshaw (Crick Advanced Light Microscopy Facility) and the Crick Fly Facility for support, and R. Etournay, M. Popovic, M. Merkel, and H. Brandl for help with Tissue Miner. We are grateful to B. Aerne for generating the UAS-HA fly stock and H. Gong, J. Frith, and B. Tapon for help with skeleton correction and image analysis. We thank J.P. Vincent and J. Briscoe for critical reading of the manuscript. J.R.D. is funded by a Sir Henry Wellcome Fellowship ( 201358/Z/16/Z ). A.F. is funded by the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement MSCA-IF-EF-ST no. 795060 . This work was supported by a Wellcome Trust Investigator award ( 107885/Z/15/Z ) to N.T. Work in the Salbreux and Tapon laboratories was supported by the Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001317 and FC001175 ), the UK Medical Research Council ( FC001317 and FC001175 ), and the Wellcome Trust ( FC001317 and FC001175 ). Funding Information: We thank Y. Bella{\"i}che, D. Bohmann, B. Stramer, K. Irvine, M. Uhlirova, and the Bloomington Drosophila Stock Centre for fly stocks. We are grateful to M. Renshaw (Crick Advanced Light Microscopy Facility) and the Crick Fly Facility for support, and R. Etournay, M. Popovic, M. Merkel, and H. Brandl for help with Tissue Miner. We are grateful to B. Aerne for generating the UAS-HA fly stock and H. Gong, J. Frith, and B. Tapon for help with skeleton correction and image analysis. We thank J.P. Vincent and J. Briscoe for critical reading of the manuscript. J.R.D. is funded by a Sir Henry Wellcome Fellowship (201358/Z/16/Z). A.F. is funded by the European Union's Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement MSCA-IF-EF-ST no. 795060. This work was supported by a Wellcome Trust Investigator award (107885/Z/15/Z) to N.T. Work in the Salbreux and Tapon laboratories was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001317 and FC001175), the UK Medical Research Council (FC001317 and FC001175), and the Wellcome Trust (FC001317 and FC001175). Conceptualization, all authors; acquisition, J.R.D. A.F. G.S. and N.T.; experiments, A.P.A. J.R.D. and A.F.; theory and simulations, J.J.W. A.T.-S. and G.S.; experimental methodology, F.M. and E.M.-B.; software, J.R.D. J.J.W. A.T.-S. A.H. and M.B.S; supervision, G.S. and N.T.; writing – original draft, A.P.A. J.R.D. J.J.W. A.F. A.H. M.B.S. G.S. and N.T.; writing – review & editing, all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors Copyright {\textcopyright} 2022 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = mar,
day = "28",
doi = "10.1016/j.cub.2022.01.045",
language = "English",
volume = "32",
pages = "1285--1300.e4",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "6",
}