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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.
Fig. 3.
Programmed cellular senescence during Xenopus laevis development. (A-K) Representative images of SAβgal staining of whole-mount Xenopus embryos at the indicated developmental stages (n=8 per stage). (A,B) Xenopus embryos, NF 46 (A) and NF 49 (B). (C) Xenopus pronephros, NF 49. (D-F) Xenopus brains at NF 46 (D), NF 49 (E) and NF 52 (F). (G-I) Xenopus anteriorcartilage at NF 46 (G), NF 49 (H) and NF 52 (I). (J,K) Xenopus pronephros at NF 46 (J) and NF 49 (K). Senescence is absent in brain and cartilage at NF 46 and NF 52. c, cartilage; cg, cement gland; hb, hindbrain; mb, midbrain; p, pronephros. Scale bars: 100 µm in C; 50 µm in D-K. (L-N) Representative cryosections of Xenopus pronephros at NF 46 (SAβgal negative, L) and NF 51 (SAβgal positive, M and N) following staining with E. cristagalli lectin, DAPI and the indicated antibodies. Scale bar: 50 µm.
Fig. 4.
Inhibition of TGFβ signalling abrogates cellular senescence in Xenopus laevis cement gland, leading to morphogenetic alterations in neighbouring structures. (A) SAβgal staining of whole-mount Xenopus embryos at NF 45 following treatment with the indicated inhibitors, from stage 24 onwards. Arrows indicate the cement gland. Positive signal is present in the control tadpoles (n=6). (B) Representative paraffin wax-embedded sections following SAβgal/Haematoxylin and Eosin co-staining. Senescent cells are absent and the cement gland is smaller in animals treated with the TGFβ inhibitor 1. Scale bar: 50 µm. (C) Quantification of number of SAβgal-positive cells per area (µm2) in NF 45 tadpoles following treatment with the indicated inhibitors, from stage 24 onwards (n=4, **P<0.01). Data are mean±s.e.m. (D) Western blot analysis of tadpole extracts following the indicated treatments. Phospho-Smad3 levels decrease only upon treatment with TGFβ inhibitor 1 (n=5). (E) Representative images of the anterior region of Xenopus embryos at NF 45 following the indicated treatments. Abrogation of cellular senescence through TGFβ inhibition results in a substantial shortening of the mouth (red dotted lines) (n=8). (F) Quantification of average mouth length in NF 46 tadpoles treated with vehicle (DMSO) or TGFβ inhibitor 1 (n=8, **P<0.01). Data are mean±s.e.m.
Acosta,
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
2013, Pubmed
Acosta,
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
2013,
Pubmed
Baker,
Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan.
2016,
Pubmed
Baker,
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.
2011,
Pubmed
Bodnar,
Extension of life-span by introduction of telomerase into normal human cells.
1998,
Pubmed
Braig,
Oncogene-induced senescence as an initial barrier in lymphoma development.
2005,
Pubmed
Brennan,
The specification of the pronephric tubules and duct in Xenopus laevis.
1998,
Pubmed
,
Xenbase
Burton,
Physiological and pathological consequences of cellular senescence.
2014,
Pubmed
Cameron,
The absence of cell death during development of free digits in amphibians.
1977,
Pubmed
,
Xenbase
Campisi,
Cellular senescence: when bad things happen to good cells.
2007,
Pubmed
Carroll,
Wilms' tumor suppressor gene is involved in the development of disparate kidney forms: evidence from expression in the Xenopus pronephros.
1996,
Pubmed
,
Xenbase
Chang,
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.
2016,
Pubmed
Chuprin,
Cell fusion induced by ERVWE1 or measles virus causes cellular senescence.
2013,
Pubmed
Collado,
Tumour biology: senescence in premalignant tumours.
2005,
Pubmed
Davidson,
Mouse kidney development
2008,
Pubmed
Demaria,
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
2014,
Pubmed
Desgrange,
Nephron Patterning: Lessons from Xenopus, Zebrafish, and Mouse Studies.
2015,
Pubmed
,
Xenbase
Dimri,
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
1995,
Pubmed
FOX,
Growth and degeneration of the pronephric system of Rana temporaria.
1962,
Pubmed
Haugan,
Functional characterization of the vertebrate primary ureter: structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia).
2010,
Pubmed
Horton,
Ontogeny of Xenopus NK cells in the absence of MHC class I antigens.
2003,
Pubmed
,
Xenbase
Hubackova,
IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'bystander senescence'.
2012,
Pubmed
Jun,
Cellular senescence controls fibrosis in wound healing.
2010,
Pubmed
Kondaiah,
Transforming growth factor-beta5 expression during early development of Xenopus laevis.
2000,
Pubmed
,
Xenbase
Krizhanovsky,
Senescence of activated stellate cells limits liver fibrosis.
2008,
Pubmed
Krtolica,
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging.
2001,
Pubmed
Kuilman,
Senescence-messaging secretome: SMS-ing cellular stress.
2009,
Pubmed
Laberge,
Epithelial-mesenchymal transition induced by senescent fibroblasts.
2012,
Pubmed
Lévesque,
Transforming growth factor: beta signaling is essential for limb regeneration in axolotls.
2007,
Pubmed
Marr,
CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes.
2005,
Pubmed
,
Xenbase
Muñoz-Espín,
Programmed cell senescence during mammalian embryonic development.
2013,
Pubmed
Nacher,
The quail mesonephros: a new model for renal senescence?
2006,
Pubmed
Nelson,
A senescent cell bystander effect: senescence-induced senescence.
2012,
Pubmed
Nye,
Extending the table of stages of normal development of the axolotl: limb development.
2003,
Pubmed
,
Xenbase
Rai,
Lessons from senescence: chromatin maintenance in non-proliferating cells.
2013,
Pubmed
Robert,
Comparative and developmental study of the immune system in Xenopus.
2009,
Pubmed
,
Xenbase
Sagiv,
Immunosurveillance of senescent cells: the bright side of the senescence program.
2013,
Pubmed
Schreckenberg,
Normal stages of development of the axolotl. Ambystoma mexicanum.
1975,
Pubmed
Serrano,
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
1997,
Pubmed
Sive,
A sticky problem: the Xenopus cement gland as a paradigm for anteroposterior patterning.
1996,
Pubmed
,
Xenbase
Sousa-Victor,
Geriatric muscle stem cells switch reversible quiescence into senescence.
2014,
Pubmed
Storer,
Senescence is a developmental mechanism that contributes to embryonic growth and patterning.
2013,
Pubmed
Tabler,
Hedgehog activity controls opening of the primary mouth.
2014,
Pubmed
,
Xenbase
van Deursen,
The role of senescent cells in ageing.
2014,
Pubmed
Villiard,
Senescence gives insights into the morphogenetic evolution of anamniotes.
2017,
Pubmed
Vize,
Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.
1997,
Pubmed
,
Xenbase
Wallingford,
p53 activity is essential for normal development in Xenopus.
1997,
Pubmed
,
Xenbase
Wingert,
The zebrafish pronephros: a model to study nephron segmentation.
2008,
Pubmed
,
Xenbase
Xue,
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas.
2007,
Pubmed
Yun,
Changes in Regenerative Capacity through Lifespan.
2015,
Pubmed
Yun,
Regulation of p53 is critical for vertebrate limb regeneration.
2013,
Pubmed
Yun,
Sustained ERK activation underlies reprogramming in regeneration-competent salamander cells and distinguishes them from their mammalian counterparts.
2014,
Pubmed
Yun,
Recurrent turnover of senescent cells during regeneration of a complex structure.
2015,
Pubmed
Zhu,
Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial infarction.
2013,
Pubmed
