title: Conserved and novel functions of programmed cellular senescence during vertebrate development.
abstract: Cellular senescence, a form of stable cell cycle arrest that is traditionally associated with tumour suppression, has been recently found to occur during mammalian development. Here, we show that cell senescence is an intrinsic part of the developmental programme in amphibians. Programmed senescence occurs in specific structures during defined time windows during amphibian development. It contributes to the physiological degeneration of the amphibian pronephros and to the development of the cement gland and oral cavity. In both contexts, senescence depends on TGFβ but is independent of ERK/MAPK activation. Furthermore, elimination of senescent cells through temporary TGFβ inhibition leads to developmental defects. Our findings uncover conserved and new roles of senescence in vertebrate organogenesis and support the view that cellular senescence may have arisen in evolution as a developmental mechanism.
authors.affiliation: Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.|Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
authors.forename: Hongorzul
authors.initials: H
authors.lastname: Davaapil
authors.affiliation: Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Brockes
authors.affiliation: Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK maximina.yun@ucl.ac.uk.
authors.forename: Maximina H
authors.identifier: 0000-0001-9019-2453
authors.initials: MH
authors.lastname: Yun
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology; D000663:Amphibians / Q000196:embryology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000196:embryology; D038081:Organogenesis / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014714:Vertebrates / Q000196:embryology*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D051017:Apoptosis Regulatory Proteins; D016212:Transforming Growth Factor beta
keywords: Axolotl; Cellular senescence; Cement gland; Kidney; TGFβ; Xenopus