Morphogen hunting in Dictyostelium.

A highly regulative pattern of prestalk and prespore tissue is formed during Dictyostelium development, starting from separate amoebae. Potential morphogens controlling this process have been hunted biochemically, using bioassays to monitor activity. All those discovered to date are low MW diffusible compounds: cAMP, adenosine, NH3 and DIFs 1-3. The DIFs are assayed by their ability to induce isolated amoebae to differentiate into stalk cells and have been identified as a family of chlorinated phenyl alkanones. The diversification of amoebae into prestalk and prespore cells seems to be brought about by cAMP and DIF-1. cAMP is necessary for both pathways of differentiation but DIF-1 specifically induces the differentiation of prestalk cells while suppressing that of prespores. When DIF-1 is added to intact slugs, it causes a substantial enlargement of the prestalk tissue at physiological concentrations in the time previously shown to be required for pattern regulation. DIF-1 is a dynamic molecule and we have found that it is metabolized along a pathway involving at least 8 compounds. Metabolism is developmentally regulated and may be important in producing DIF gradients or other effector molecules from DIF. Although we almost certainly have some of the central actors, it is difficult to formulate a satisfactory theory of pattern formation in Dictyostelium at the moment. We suspect that at least one important actor is missing.