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Development 128, 4959-4966 (2001)
© 2001 The Company of Biologists Limited

Cross-induction of cell types in Dictyostelium: evidence that DIF-1 is made by prespore cells

Robert R. Kay* and Christopher R. L. Thompson

MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

*Author for correspondence (e-mail: rrk{at}mrc-lmb.cam.ac.uk)

Accepted September 26, 2001

To investigate how cell type proportions are regulated during Dictyostelium development, we have attempted to find out which cell type produces DIF-1, a diffusible signal molecule inducing the differentiation of prestalk-O cells. DIF-1 is a chlorinated alkyl phenone that is synthesized from a C12 polyketide precursor by chlorination and methylation, with the final step catalysed by the dmtA methyltransferase. All our evidence points to the prespore cells as the major source of DIF-1. (1) dmtA mRNA and enzyme activity are greatly enriched in prespore compared with prestalk cells. The chlorinating activity is also somewhat prespore-enriched. (2) Expression of dmtA is induced by cyclic-AMP and this induction is inhibited by DIF-1. This regulatory behaviour is characteristic of prespore products. (3) Short-term labelling experiments, using the polyketide precursor, show that purified prespore cells produce DIF-1 at more than 20 times the rate of prestalk cells. (4) Although DIF-1 has little effect on its own synthesis in short-term labelling experiments, in long-term experiments, using 36Cl– as label, it is strongly inhibitory (IC50 about 5 nM), presumably because it represses expression of dmtA; this is again consistent with DIF-1 production by prespore cells. Inhibition takes about 1 hour to become effective.

We propose that prespore cells cross-induce the differentiation of prestalk-O cells by making DIF-1, and that this is one of the regulatory loops that sets the proportion of prespore-to-prestalk cells in the aggregate.

Key words: Dictyostelium, DIF-1, Proportioning mechanism, Cell differentiation


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© The Company of Biologists Ltd 2001