Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

Cellular senescence (cells that are still alive but cannot divide anymore) has been widely studied in plants and is associated with leaf color change. In animals, cellular senescence has been, until recently, exclusively associated with aging and as a mean to prevent aberrant cellular proliferation similar to apoptosis (organized process of cell death). Interestingly senescence is in some ways similar to apoptosis in that it is a process that evolved to eliminate cells from a cycling population and is highly programmed. Cells that become senescent stop proliferating and start to secrete multiple cytokines (small secreted proteins that affect surrounding cells) that can act as growth factors and immunomodulators on surrounding tissues. There has been thus far no cellular processes that have been observed in mature organisms that are completely absent from developing embryos (cell division, differentiation, asymmetric division, migration and apoptosis). Therefore it was not entirely surprising when the groups of Serrano and Keyes independently published their research showing for the first time that cellular senescence is important for normal development in mice. This is of interest in terms of understanding differences observed during the developmental process in vertebrates. If we take the process of limb development as an example, it has been clearly shown that apoptosis is important to eliminate the cells between the digits in mice and chicken in order to yield web free hands/feet. However, amphibians will develop limbs free of webbed hands without apoptosis between the fingers. How do amphibians eliminate those cells if it is not apoptosis? These are the types of questions that could be answered by taking an evo-devo approach in studying the role of cellular senescence during embryonic development. This proposal aims to establish a research program to unravel the developmental role of cellular senescence in vertebrates in order to provide a better understanding of the how it may influence patterning and growth.
Hypotheses
1- Senescence is important during early development and pattern formation in amphibians.
2- Senescence is important during the process of metamorphosis in vertebrates.
Specific Objectives for the next 5 years
1- To characterize and assess the role of senescence throughout the developmental process.
2- To characterize and assess the role of senescence during metamorphosis in salamanders.
3- To develop transgenic (genetically modified) lines of axolotls using the p21 and p16ink4a promoters to drive the expression of mcherry as a reporter for the detection of cellular senescence in vivo.
The proposed program will provide in depth analysis to establish which signalling pathways are important for the regulation of cellular senescence during embryogenesis and metamorphosis.