THE POSTMITOTIC STATE OF TERMINALLY DIFFERENTIATED CELLS: UNDERLYING MECHANISMS AND OVERRIDING STRATEGIES

The long-term aim of this project is to make possible to replace diseased cells in organs unable to self-repair. The nervous system, heart, and many endocrine glands belong to this category, as their cells cannot proliferate. The proponent's group have previously discovered that the expression of specific genes (cyclin D1 and cdk4) in cells otherwise unable to replicate (terminally differentiated cells) can reactivate proliferation. Thus, we propose to investigate how such reactivation takes place in order to understand the mechanisms that make some cells permanently unable to proliferate. It has recently been discovered that a gene named msx1 can induce terminally differentiated muscle cells to proliferate. Thus, we propose to verify and confirm this result and investigate its potential in view of possible therapeutic applications.