Notch and Prospero maintain the terminal quiescent state.
In spite of their pertinence, the questions of how proliferation is arrested in developmentally regulated cell lineages and in particular, how cells maintain their terminal quiescent state upon lineage completion remain unanswered. We have addressed these questions in the bristle lineage in which terminal cells are formed after three rounds of cell divisions. To this end, we have tested the capacity of post-mitotic cells to re-enter the cell cycle in response to the overexpression of CycE, a procedure used to mimic proliferative conditions. Surprisingly, not all cells in the lineage respond in the same way to proliferative signals. In fact, only the shaft cell and the neurone performed additional cell divisions after CycE overexpression. Interestingly, the Notch pathway is not activated in these two terminal cells. As such, we hypothesised that the activation of the Notch-pathway maintains cells in an arrested state which explains why only terminal cells in which the identity does not depend on the activation of the Notch pathway undergo extra divisions upon CycE overexpression. Indeed, our analysis shows that the responsiveness of cells to forced proliferation depends on the level of Notch pathway activity. In addition, we revealed that Prospero, a fate determinant highly expressed in the sheath cell, was also involved in this differential sensitivity to cell proliferation. We observed that: (1) the number of sheath cells and neurones exhibiting extra cell divisions was increased in a pros17/+ background; (2) activation of the N pathway blocked the division of the shaft cell; (3) socket cells underwent an extra division after reduction of N pathway activity and (4) more sheath cells underwent extra divisions when both N and Pros activity were reduced. ￼Since all of these observations were obtained with no cell transformation, these results show that the N pathway and Pros have an anti-mitotic action in terminal cells of the bristle lineage. Our results demonstrate that factors involved in fate determination such as the Notch pathway and Prospero also participate in maintaining a quiescent state in terminal cells of the bristle lineage. Thus, the terminal quiescent state and differentiation are regulated by two parallel mechanisms acting simultaneously on fate acquisition and cell cycle progression. This work is the subject of a published manuscript (Simon F, Fichelson P, Gho M & Audibert A (2009) PLoS Genet. 8:e1000594).