A model for regulation of cell-type proportions in the mound stage of the cellular slime mold Dictyostelium discoideum has been developed. The model is based on current information about morphogenetic signaling that controls the differentiation of prestalk and prespore cells from differentiation-competent cells. The morphogens that can control the cell-type transitions are: (i) cAMP, which is required for both prestalk and prespore differentiation, (ii) differentiation-inducing factor (DIF), which induces prestalk and inhibits prespore differentiation, and (iii) NH3, which antagonizes all DIF-induced responses. cAMP is assumed to be a background species at the mound stage produced by oscillatory cAMP signaling. In addition to its effects on differentiation, cAMP also induces DIF synthesis. DIF levels are controlled by DIF-dechlorinase, which is produced by the prestalk population in response to DIF stimulation. Induction of DIF-dechlorinase is inhibited by cAMP and NH3. NH3 is produced by prestalk cells, which show relatively high catabolism. As far as possible, we have incorporated quantitative information on transition rates between cell types and the dependence of those rates on the morphogen concentrations. Computations using these data produce correct proportions of prestalk cells, but yield a ratio of prespore to undifferentiated cells that is too low. This can be remedied by assuming that maintenance of prespore differentiation requires a 10-fold lower cAMP concentration than induction. In the absence of NH3 and DIF-dechlorinase production, all cells rapidly differentiate into prestalk cells. DIF-dechlorinase is of major importance in setting prestalk and prespore proportions, but inclusion of NH3 in the presence of DIF-dechlorinase is not strictly necessary in the spatially uniform system studied here. The regulatory capacity of the system is very robust, and proportion regulation is not very sensitive to changes in morphogen concentrations, beyond a certain level required for differentiation induction.
|Original language||English (US)|
|Number of pages||16|
|State||Published - Jan 1 1996|