Abstract
Throughout growth and development,Dictyostelium cells secrete autocrine factors that accumulate in proportion to cell density. At sufficient concentration, these factors cause changes in gene expression. VegetativeDictyostelium cells continuously secrete prestarvation factor (PSF). The bacteria upon which the cells feed inhibit their response to PSF, allowing the cells to monitor their own density in relation to that of their food supply. At high PSF/bacteria ratios, which occur during late exponential growth, PSF induces the expression of several genes whose products are needed for cell aggregation. When the food supply has been depleted, PSF production declines, and a second density-sensing pathway is activated. Starving cells secrete conditioned medium factor (CMF), a glycoprotein of Mr 80 kDa that is essential for the development of differentiated cell types. Antisense mutagenesis has shown that cells lacking CMF cannot aggregate, and preliminary data suggest that CMF regulates cAMP signal transduction. Calculations indicate that a mechanism of simultaneously secreting and recognizing a signal molecule, as used byDictyostelium to monitor cell density, could also be used to determine the total number of cells in a tissue.
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Ashworth, J.M., and Quance, J., Enzyme synthesis in myxamoebae of the cellular slime mouldDictyostelium discoideum during growth in axenic culture. Biochem. J.126 (1972) 601–608.
Berks, M., Traynor, D., Carrin, I., Insall, R.H., and Kay, R.R., Diffusible signal molecules controlling cell differentiation and patterning inDictyostelium. DevelopmentSuppl. 1 (1991) 131–139.
Blusch, J., Morandini, P., and Nellen, W., Transcriptional regulation by folate-inducible gene expression inDictyostelium transformants during growth and early development. Nucleic Acids Res.20 (1992) 6235–6238.
Brenner, M., and Thoms, S.D., Caffeine blocks activation of cyclic AMP synthesis inDictyostelium discoideum, Devl Biol.101 (1984) 136–146.
Brookman, J.J., Jermyn, K.A., and Kay, R.R., Nature and distribution of the morphogen DIF in theDictyostelium slug. Development100 (1987) 119–124.
Burdine, V., and Clarke, M., Genetic and physiologic modulation of the prestarvation response inDictyostelium discoideum. Molec. biol. Cell6 (1995) 311–325.
Burns, R.A., Livi, G.P., and Dimond, R.L., Regulation and secretion of early developmentally controlled enzymes during axenic growth inDictyostelium discoideum. Devl Biol.84 (1981) 407–416.
Clarke, M., Dominguez, N., Yuen, I.S., and Gomer, R.H., Growing and starvingDictyostelium cells produce distinct density-sensing factors. Devl Biol.152 (1992) 403–406.
Clarke, M., Kayman, S.C., and Riley, K., Density-dependent induction of discoidin-I synthesis in exponentially growing cells ofDictyostelium discoideum. Differentiation34 (1987) 79–87.
Clarke, M., Yang, J., and Kayman, S., Analysis of the prestarvation response in growing cells ofDictyostelium discoideum. Devl Genet.9 (1988) 315–326.
Cotter, D.A., Sands, T.W., Virdy, K.J., North, M.J., Klein, G., and Satre, M., Patterning of development inDictyostelium discoideum. Factors regulating growth, differentiation, spore dormancy, and germination. Biochem. Cell Biol.70 (1992) 892–919.
Das, O.P., and Henderson, E.J., A novel technique for gentle lysis of eukaryotic cells isolation of plasma membranes fromDictyostelium discoideum. Biochim. biophys. Acta736 (1983) 45–56.
Faure, M., Franke, J., Hall, A.L., Podgorski, G.J., and Kessin, R.H., The cyclic nucleotide phosphodiesterase gene ofDictyostelium discoideum contains three promoters specific for growth, aggregation, and late development. Molec. cell. Biol.10 (1990) 1921–1930.
Fontana, D.R., Price, P.L., and Phillips, J.C., Cell-cell contact mediates cAMP secretion inDictyostelium discoideum. Devl Genet.12 (1991) 54–62.
Franke, J., Podgorski, G.J., and Kessin, R.H., The expression of two transcripts of the phosphodiesterase gene during the development ofDictyostelium discoideum. Devl Biol.124 (1987) 504–511.
Gerisch, G., and Wick, U., Intracellular oscillations and release of cyclic AMP fromDictyostelium cells. Biochem. biophys. Res. Commun.65 (1975) 364–370.
Gomer, R., Datta, S., Mehdy, M., Crowley, T., Sivertson, A., Nellen, W., Reymond, C., Mann, S., Firtel, R.A., Regulation of cell-type specific gene expression inDictyostelium. Cold Spring Harb. Symp. quant. Biol.50 (1985) 801–812.
Gomer, R.H., and Firtel, R.A., Cell-autonomous determination of cell-type choie inDictyostelium development by cellcycle phase. Science237 (1987) 758–762.
Gomer, R.H., and Lazarides, E., Switching of filamin polypeptides during myogenesis in vitro. J. Cell Biol.96 (1983) 321–329.
Gomer, R.H., Yuen, I.S., and Firtel, R.A., A secreted 80×103 Mr proteins mediates sensing of cell density and the onset of development inDictyostelium. Development112 (1991) 269–278.
Goodloe-Holland, C.M., and Luna, E.J., Purification and characterization ofDictyostelium discoideum plasma membranes, in: Methods in Cell Biology, pp. 103–128. Ed. J.A. Spudich. Academic Press, Orlando, Florida, 1987.
Grabel, L., and Loomis, W.F., Effector controlling accumulation of N-acetylglucosaminidase during development ofDictyostelium discoideum. Devl Biol.64 (1978) 203–209.
Grossman, A.D., and Losick, R., Extracellular control of spore formation inBacillus subtilis. Proc. natl Acad. Sci. USA85 (1988) 4369–4373.
Hanna, M.H., and Cox, E.C., The regulation of cellular slime mold development: A factor causing development ofPolysphondylium violaceum aggregation defective mutants. Devl Biol.62 (1978) 206–214.
Hanna, M.H., Fatone, M.A., Nowicki, J.J., and Arnal, F., Developmental regulation of production of an aggregationstimulating factor from the cellular slime moldPolysphondylium violaceum. Differentiation26 (1984) 97–102.
Jain, R., and Gomer, R.H., A developmentally regulated cell surface receptor for a density-sensing factorDictyostelium. J. biol. Chem.269 (1994) 9128–9136.
Jain, R., Gomer, R.H., and Murtagh, Jr, J.J., Increasing specificity from the PCR-RACE technique. BioTechniques12 (1992) 58–59.
Jain, R., Yuen, I.S., Taphouse, C.R., and Gomer, R.H., A density-sensing factor controls development inDictyostelium. Genes Devl.6, (1992) 390–400.
Janssens, P.M.W., Van der Geer, P.J.L., Arents, J.C., and Van Driel, R., Guanine nucleotides modulate the function of chemotactic cyclic AMP receptors inDictyostelium discoideum. Molec. cell. Biochem.67 (1985) 119–124.
Kay, R.R., Gene expression inDictyostelium discoideum: mutually antagonistic roles of cyclic AMP and ammonia. J. Embryol. expl. Morphol.52 (1979) 171–182.
Kim, S.K., and Kaiser, D., C-factor: Cell-cell signaling protein required for fruiting body morphogenesis ofM. xanthus. Cell61 (1990) 19–26.
Kim, S.K., and Kaiser, D., Cell motility is required for the transmissioin of C-factor, an intercellular signal that coordinates fruiting body morphogenesis ofMyxococcus xanthus. Genes Devl.4 (1990) 896–905.
Kimmel, A.R., and Firtel, R.A., The organization and expression of theDictyostelium genome, in: Development ofDictyostelium discoideum, pp. 233–324. Ed. W.F. Loomis. Academic Press, New York, 1982.
Klein, C., and Darmon, M., A differentiation stimulating factor induces cell sensitivity to 3′:5′-cyclic AMP pulses inDictyostelium discoideum. Proc. natl Acad. Sci. USA73 (1976) 1250–1254.
Klein, C., and Darmon, M., Effects of cAMP on adenylate cyclase and the phosphodiesterase ofDictyostelium discoideum. Nature, Lond.268 (1977) 76–78.
Liu, T.Y., Williams, J.G., and Clarke, M., Inducible expression of calmodulin antisense RNA inDictyostelium cells inhibits the completion of cytokinesis. Molec. biol. Cell3 (1992) 1403–1413.
Luo, Q., Michaelis, C., and Weeks, G., Overexpression of a truncated cyclin B gene arrestsDictyostelium cell division in mitosis. J. Cell Sci.107 (1994) 3105–3114.
Marin, F.T., Regulation of development inDictyostelium discoideum: I. initiation of the growth to developmental transition by amino acid starvation. Devl Biol.48 (1976) 110–117.
McDonald, S.A., and Durston, A.J., The cell cycle and sorting behavior inDictyostelium discoideum. J. Cell Sci.66 (1984) 195–204.
Mehdy, M.C., and Firtel, R.A., A secreted factor and cyclic AMP jointly regulate cell-type-specific gene expression inDictyostelium discoideum. Molec. cell. Biol.5 (1985) 705–713.
Mierendorf, R.C., Cardelli, J.A., Livi, G.P., and Dimond, R.L., Synthesis of related forms of the lysosomal enzyme α-mannosidase inDictyostelium discoideum. J. biol. Chem.258 (1983) 5878–5884.
Rathi, A., and Clarke, M., Expression of early developmental genes inDictyostelium discoideum is initiated during exponential growth by an autocrine-dependent mechanism. Mechanisms of Development36 (1992) 173–182.
Rathi, A., Kayman, S.C., and Clarke, M., Induction of gene expression inDictyostelium by prestarvation factor, a factor secreted by growing cells. Devl Genet.12 (1991) 82–87.
Reymond, C.D., Gomer, R.H., Mehdy, M.C., and Firtel, R.A., Developmental regulation of aDictyostelium gene encoding a protein homologous to mammalian ras protein. Cell39 (1984) 141–148.
Reymond, C.D., Gomer, R.H., Nellen, W., Theibert, A., Devreotes, P., and Firtel, R., Phenotypic changes induced by a mutatedras gene during the development ofDictyostelium transformants. Nature, Lond.323 (1986) 340–343.
Saxe, C.L., Johnson, R.L., Devreotes, P.N., and Kimmel, A.R., Expression of a cAMP receptor gene ofDictyostelium and evidence for a multigene family. Genes Devl.5 (1991) 1–8.
Schaap, P., and Wang, M., Interactions between adenosine and oscillatory cAMP signaling regulate size and pattern inDictyostelium. Cell45 (1986) 137–144.
Schaller, K.L., Leichtling, B.H., Majerfeld, I.H., Woffendin, C., Spitz, E., Kakinuma, S., and Rickenberg, H.V., Differential cellular distribution of cAMP-dependent protein kinase during development ofDictyostelium discoideum. Proc natl Acad. Sci. USA81 (1984) 2127–2131.
Schatzle, J., Bush, J., Dharmawardhane, S., Firtel, R.A., Gomer, R.H., and Cardelli, J., Characterization of the signal transduction pathways and cis-acting DNA sequence responsible for the transcriptional induction during growth and development of the lysosomal α-mannosidase gene inDictyostelium discoideum. J. biol. Chem.268 (1993) 19632–19639.
Schatzle, J., Rathi, A., Clarke, M., and Cardelli, J.A., Developmental regulation of the α-mannosidase gene inDictyostelium discoideum-Control is at the level of transcription and is affected by cell density. Molec. cell. Biol.11 (1991) 3339–3347.
Sternfeld, J., and David, C.N., Ammonia plus another factor are necessary for differentiation in submerged clumps ofDictyostelium. J. Cell Sci.38 (1979) 181–191.
Sun, T.J., and Devreotes, P.N., Gene targeting of the aggregation stage cAMP receptor cAR1 inDictyostelium. Genes Devl.5 (1991) 572–582.
Van Haastert, P.J.M., de Wit, R.J.W., Janssens, P.M.W., Kesbeke, F., and de Goede, J., G-protein-mediated interconversions of cell-surface cAMP receptors and their involvement in excitation and desensitization of guanylate cyclase inDictyostelium discoideum. J. biol. Chem.261 (1986) 6904–6911.
Van Hasstert, P.J.M., Jastorff, B., Pinas, J.E., and Konijn, T.M., Analogs of cyclic AMP as chemoattractant and inhibitors ofDictyostleium chemotaxis. J. Bact.149 (1982) 99–105.
Vauti, F., Morandini, P., Blusch, J., Sachse, A., and Nellen, W., Regulation of the discoidin-I gamma-gene inDictyostelium discoideum-identification of individual promoter elements mediating induction of transcription and repression by cyclic AMP. Molec. cell. Biol.10 (1990) 4080–4088.
Wang, M., Van Haastert, P.J.M., and Schaap, P., Multiple effects of differentiation-inducing factor on prespore differentiation and cyclic-AMP signal transduction inDictyostelium. Differentiation33 (1986) 24–28.
Weijer, C.J., Duschl, G., and David, C.N., Dependence of cell-type proportioning and sorting on cell cycle phase inDictyostelium discoideum. J. Cell Sci.70 (1984) 133–145.
Whitbread, J.A., Sims, M., and Katz, E.R., Evidence for the presence of a growth factor inDictyostelium discoideum. Devl Genet.12 (1991) 78–81.
Williams, J.G., The role of diffusible molecules in regulating the cellular differentiation ofDictyostelium discoideum. Development103 (1988) 1–16.
Yuen, I.S., and Gomer, R.H., Cell density-sensing inDictyostelium by means of the accumulatioin rate, diffusion coefficient and activity threshold of a protein secreted by starved cells. J. Theor. Biol.167 (1994) 273–282.
Yuen, I.S., Taphouse, C., Halfant, K.A., and Gomer, R.H., Regulation and processing of a secreted protein that mediates sensing of cell density inDictyostelium. Development113 (1991) 1375–1385.
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Clarke, M., Gomer, R.H. PSF and CMF, autocrine factors that regulate gene expression during growth and early development ofDictyostelium. Experientia 51, 1124–1134 (1995). https://doi.org/10.1007/BF01944730
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DOI: https://doi.org/10.1007/BF01944730