New roles for DIF? Effects on early development in Dictyostelium.

The DIFs are unusual, chlorinated molecules which induce stalk cell differentiation during the later, multicellular phase of Dictyostelium development. Here we provide evidence that one or more DIFs have a role during early development, when small amounts are known to be made. Initial indications came from an optical technique which detects changes in shape or cohesion of cells in suspension (Gerisch and Hess, PNAS 71, 2118, 1974). After a period of optical inactivity at the start of development, cell suspensions normally produce spontaneous spike-shaped light-scattering oscillations synchronised by oscillations in extracellular cAMP levels, followed by sinusoidal oscillations where the synchroniser is not known. DIFs 1 and 2 produce optical responses from cells at all these early stages of development. The phase of both spiked and sinusoidal oscillations can be shifted, indicating an effect on the oscillator in each case. We find further: (1) cAMP oscillations and cAMP relay during spiked oscillations are transiently inhibited by DIF-1. (2) DIF-1 causes a transient decrease in cellular cGMP levels in cells taken before oscillations commence and likewise inhibits the cGMP response to a cAMP stimulus in cells taken later in development. Cytoskeletal organization and hence cell shape might be affected by DIF-1 by this indirect route. (3) The effects of DIF-1 are transient, even though it is essentially stable in the cell suspension. Cells somehow adapt to DIF-1. (4) The effects are chemically specific: DIF-1 and DIF-2 are active at 10(-7) to 10(-8) M, with DIF-2 being the more active, whereas related compounds have little or no activity at 10(-6) M. These results indicate that cells are responsive to DIFs 1 and 2 from the start of development and suggest a wider role for the DIFs. This role might involve effects on cAMP signalling and on intracellular second messengers.