Abstract
Cellular senescence is considered a stress response imposing a stable cell cycle arrest to restrict the growth of damaged cells. More recently however, cellular senescence was identified during mouse embryo development at particular structures during specific periods of time. This programmed cell senescence has been proposed to serve developmental and morphogenetic functions and to potentially represent an evolutionary origin of senescence. Cellular senescence has also been described to take place during bird (chick and quail) and amphibian (xenopus and axoltl) development. Fish however, have been described to show a very narrow and restricted pattern of developmental cell senescence. Here we carried out a detailed characterization of senescence during zebrafish development and found it to be conserved and widespread. Apart from yolk and cloaca, previously described structures, we also identified senescence in the developing central nervous system, intestine, liver, pronephric ducts, and crystalline. Interestingly, senescence at these developing structures disappeared upon treatment with senolytic compound ABT-263, supporting their senescent identity and opening the possibility of studying the contribution of this process to development. In summary, our findings extend the description of developmentally-programmed cell senescence to lower vertebrates contributing to the notion of the relevance of this process for embryo development.
Highlights
Cellular senescence is a state of permanent cell cycle arrest imposed on cells upon a wide range of potentially dangerous stressors and serving as a potent tumour suppressor mechanism [1, 2]
Several studies reported the occurrence of cellular senescence in developing tissues of mammals, birds and amphibians in non-pathological conditions raising the possibility of an evolutionary origin of senescence as a positive morphogenetic and tissue remodelling force operating during development [3,4,5,6]
In whole-mounts, the intensity of SA–β–gal staining was weaker in 2 dpf animals and increased as development progressed, with the strongest intensity observed from 7 dpf onwards (Figure 1)
Summary
Cellular senescence is a state of permanent cell cycle arrest imposed on cells upon a wide range of potentially dangerous stressors and serving as a potent tumour suppressor mechanism [1, 2]. Several studies reported the occurrence of cellular senescence in developing tissues of mammals (mice and humans), birds (chick and quail) and amphibians (xenopus and axoltl) in non-pathological conditions raising the possibility of an evolutionary origin of senescence as a positive morphogenetic and tissue remodelling force operating during development [3,4,5,6]. In this sense, the presence of cellular senescence during the early development of zebrafish was reported recently [7]. We carried out a careful examination of the occurrence of SA– β–gal staining in developing zebrafish and found it to be widespread in a number of developing structures
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