Effector caspase activation is a critical regulatory step in apoptosis, as well as an essential inductive cut in numerous non-death related processes that occur within complex cell systems. Here we report two novel studies detailing mechanisms by which effector caspase activation advances muscle cell differentiation. In the first study, we demonstrate that caspase 3 triggered DNA damage leads to rapid formation of XRCC1 repair foci within differentiating myonuclei, which dissipates as the maturation program proceeds. Skeletal myoblast deletion of XRCC1 does not impact cell growth, yet leads to perinatal lethality, with sustained DNA damage and impaired myofiber development. These observations demonstrate that the temporal deployment of the XRCC1-related DNA repair mechanisms are effector caspase mediated, and essential for muscle cell differentiation. In the second study, we sought to investigate whether effector caspase enzymes altered chromatin structure to promote the early differentiation of muscle progenitor cells. Past research has shown that Matrix Attachment region proteins known as Special AT-rich binding proteins are expressed abundantly in stem and progenitor cells, showing rapid decrease in expression as the cell advances into its mature phenotype. Here we demonstrate that effector caspase-7 is responsible for cleavage of Satb2, rather than caspase 3. Satb2 degradation alters the expressed genetic profile leading to acceleration of the muscle differentiation program. Our cumulative work adds novel roles in which effector caspases are vital in the development of cells.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/36909 |
| Date | January 2017 |
| Creators | Al-Khalaf, Mohammad |
| Contributors | Megeney, Lynn |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0021 seconds