Cell-cycle checkpoint for transition from cell division to differentiation

Abstract

In general, growth and differentiation are mutually exclusive, but they are cooperatively regulated during the course of development. Thus, the process of a cell's transition from growth to differentiation is of general importance for the development of organisms, and terminally differentiated cells such as nerve cells never divide. Meanwhile, the growth rate speeds up when cells turn malignant. The cellular slime mold Dictyostelium discoideum grows and multiplies as long as nutrients are supplied, and its differentiation is triggered by starvation. A critical checkpoint (growth/differentiation transition or GDT point), from which cells start differentiating in response to starvation, has been precisely specified in the cell cycle of D. discoideum Ax-2 cells. Accordingly, integration of GDT point-specific events with starvation-induced events is needed to understand the mechanism regulating GDTs. A variety of intercellular and intracellular signals are involved positively or negatively in the initiation of differentiation, making a series of cross-talks. As was expected from the presence of the GDT point, the cell's positioning in cell masses and subsequent cell-type choices occur depending on the cell's phase in the cell cycle at the onset of starvation. Since novel and multiple functions of mitochondria in various respects of development including the initiation of differentiation have been directly realized in Dictyostelium cells, they are also reviewed in this article.