Eukaryotic Cell
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EC Accepts, published online ahead of print on 28 September 2007
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Eukaryotic Cell doi:10.1128/EC.00223-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Developmental Commitment in Dictyostelium discoideum

Mariko Katoh, Guokai Chen, Emily Roberge, Gad Shaulsky*, and Adam Kuspa

Department of Molecular and Human Genetics, Graduate Program in Molecular and Human Genetics, Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

* To whom correspondence should be addressed. Email: gadi{at}bcm.tmc.edu.


   Abstract

Upon starvation, Dictyostelium cells halt cell proliferation, aggregate into multicellular organisms, form migrating slugs and undergo morphogenesis into fruiting bodies while differentiating into dormant spores and dead stalk cells. At almost any developmental stage cells can be forced to dedifferentiate when they are dispersed and diluted into nutrient broth. However, migrating slugs can traverse lawns of bacteria for days without dedifferentiating, ignoring abundant nutrients and continuing development. We now show that developing Dictyostelium cells revert to the growth phase only when bacteria are supplied during the first 4-6 hours of development, but after this time, cells continue to develop regardless of the presence of food. We postulate that the cells' inability to revert to the growth phase after 6 hours represents a commitment to development. We show that the onset of commitment correlates with the cells' loss of phagocytic function. By examining mutant strains, we also show that commitment requires extracellular cAMP signaling. Moreover, cAMP pulses are sufficient to induce both commitment and the loss of phagocytosis in starving cells, whereas starvation alone is insufficient. Finally, we show that inhibition of development by food prior to commitment is independent of contact between the cells and the bacteria and that small soluble molecules, probably amino acids, inhibit development first few hours and subsequently the cells become unable to react to the molecules and commit to development. We propose that commitment serves as a checkpoint that ensures the completion of cooperative aggregation of developing Dictyostelium cells once it has begun, dampening the response to nutritional cues that might inappropriately block development.







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