DEVELOPMENTAL GENETICS 12:63-64 (1991)
Dictyostelium discoideum: A Simple Eukaryotic Microorganism With a Complex Network of Regulation DAPHNE D. BLUMBERG Department of Biological Sciences, University of Maryland, Baltimore
Key words: Development, differentiation, gene expression
Dictyostelium discoideum is a soil microorganism, which normally grows by ingesting bacteria [for a review of the life cycle see Loomis, 19751. Cell proliferation ceases when differentiation begins. Dictyostelium uses a number of well-characterized secreted factors to direct various aspects of its developmental cycle [reviewed in Williams, 19881. Here two groups, Whitbread et al. and Rathi et al., describe secreted factors which are produced by growing cells. The work of Whitbread et al. describes a putative growth factor which appears to function primarily to stimulate cell proliferation. By contrast, the factor described by Clark's group, pre-starvation factor, is continuously secreted by growing cells and is shown to induce the accumulation of certain proteins and mRNAs previously thought to be induced by starvation as Dictyostelium cells enter the developmental cycle. Although preliminary data suggests t h a t these factors are different further characterization will be necessary to determine if their activities are entirely distinct. The transition from growth to development is accompanied by a number of changes in gene expression [reviewed in Kessin, 19881. Singleton and his coworkers have described two different groups of growth phase genes, V genes and H genes. Both groups of genes are inactivated a t the onset of development by a reduction in their transcription rate [Singleton et al., 19871. Here their structure, expression, and regulation is reviewed. Interestingly, two of the V genes are demonstrated to encode ribosomal proteins. The regulation of ribosomal protein gene expression has been extensively studied by Steel and Jacobson [reviewed in Steel and Jacobson, 19881. Post-transcriptional controls, in particular, controls which regulate the translational activity of the ribosomal protein mRNAs, have been previously described by Steel and Jacobson. Here they extend these studies to define a sequence in the 5'-untranslated region of one of the ribosomal protein mRNAs which is responsible for its translational activity. Cyclic AMP orchestrates the developmental cycle in Dictyostelium. The cells secrete and use cAMP as a n
O 1991 WILEY-LISS, INC.
attractant during the aggregation stage to direct the chemotaxis of cells into multicellular mounds [reviewed in Devreotes, 19891. As the cells assemble into mounds cAMP is again used to induce the expression of many genes specific to the prespore and prestalk cells [reviewed in Blumberg et al., 19881. Finally, there is increasing evidence that cAMP may also direct the series of morphogenetic changes that shape the final fruiting body during the terminal stages of cellular differentiation [reviewed in Schaap, 19861. In order to carry out these diverse functions, developing cells express a family of cAMP receptors on their surfaces [see articles in this volume by Devreotes and Kimmell. These receptors detect cAMP in both pulsatile and continuous modes. The enzyme cyclic nucleotide phosphodiesterase and its glycoprotein inhibitor interact to regulate the levels of extracellular cAMP available to interact with receptor [reviewed in Kessin, 19881. The genes encoding both of these enzymes have been cloned by the Kessin laboratory [see Lacombe et al., 1986; Wu and Franke, 19901. Franke and coworkers review here the structure and expression of these two genes and provide insight to the complex nature of the developmental regulation of these genes. The developmental regulation of another important group of enzymes, the cysteine proteinases, is reviewed by North and Cotter. The mechanism by which cAMP regulates the expression of the prespore genes has been extensively studied (see Developmental Genetics, 1988, vol. 9, for a comprehensive review). It has been established that concomitant protein synthesis is required for cAMP mediated gene expression [see Mehdy et al., 19831. Here Ratner and coworkers [Benedict et al.] demonstrate that transcription of these genes requires protein synthesis. The cAMP regulated prespore genes were initially studied a s a group of coordinately regu-
Received for publication July 31, 1990 Address reprint requests to Daphne D. Blumberg, Dept. of Biological Science, Univ. of Maryland, Baltimore, MD 21228.
64
BLUMBERG
lated mRNAs defined by genomic and cDNA clones [see Chung et al., 1981; Mehdy et al., 1983; Barklis and Lodish, 1983; Chisholm et al., 1984; Oyama and Blumberg, 19861. What was lacking was a knowledge of the developmental function of the protein products of these genes. Here Fosnaught and Loomis show that three of the genes which encode spore coat proteins are among this group of cAMP regulated prespore genes. The culmination of the developmental cycle results in a sorocarp of spore cells held atop a slender shaft of stalk cells. Under appropriate conditions the spore will germinate. Ennis’s group has identified and cloned a number of genes expressed at specific stages of spore germination [reviewed in Ennis et al., 19881.Here they describe a very unusual family of germination specific genes. These genes encode proteins which contain a long internal tetrapeptide repeat that is conserved among all of the genes in the group but otherwise the proteins share no other homology. The papers in this section clearly demonstrate the broad spectrum of regulatory phenomena that are involved in guiding this very simple eukaryotic microorganism through its distinct phases of growth, starvation, aggregation, differentiation, and finally the germination of the spores to restart the whole cycle.
REFERENCES Barklis E, Lodish HF (1983):Regulation of Dictyostelium discoideum mRNAs specific for prespore and prestalk cells. Cell 32:1139-1148. Blumberg DD, Comer, JF Higinbotham, KG (1988): A Ca2+ dependent signal transduction system participates in coupling expression of some CAMP-dependent prespore genes to the cell surface receptor. Dev Genet 9:359-369.
Chisholm RL, Barklis E, Lodish HF (1984): Mechanism of sequential induction of cell-type specific mRNAs in Dictyostelium discoideum. Nature 310:67-69. Chung S,Landfear SM, Blumberg DD, Cohen NS, Lodish HF (1981): Synthesis and stability of developmentally regulated Dictyostelium mRNAs are affected by cell-cell contact and CAMP. Cell 24:785797. Devreotes P (1989): Dictyostelium discoideum: A model system for cell-cell interactions in development. Science 245:1054-1058. Ennis HL, Giorda R, Ohmachi T, Shaw DR (1988):Characterization of genes that are developmentally regulated during Dictyostelzum spore germination. Dev Genet 9:303-313. Kessin RH (1988): Genetics of early Dictyostelium dzscoideum development. Microbiol Rev 52:29-49. Lacombe ML, Podgorski GJ, Franke J, Kesssin RH (1986): Molecular cloning and developmental expression of the cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum. J Biol Chem 261: 16811-16817. Loomis WF (1975):“Dictyostelzum discoideum: A Developmental System.” New York Academic press. Mehdy MC, Ratner D, Firtel RA (1983): Induction and modulation of cell type specific gene expression in Dictyostelium. Cell 32:763-771. Oyama M, Blumberg DD (1986): Changes during differentiation in requirements for cAMP for expression of cell type specific mRNA accumulation in Dzctyostelium discoideum. Dev Biol 117550-556. Schaap P (1986): Regulation of size and pattern in the cellular slime molds. Differentiation 33:l-16. Singleton CK, Delude RL, McPherson CE (1987): Characterization of genes which are deactivated upon the onset of development in Dictyostelium discozdeum. Dew Biol 119t433-441. Steel LF, Jacobson A (1988): Post-transcriptional regulation of ribosomal protein gene expression during development in Dictyosteliun discoideum. Dev Genet 9:421-434. Williams J G (1988):The role of diffusible molecules in regulating the cellular differentiation of Dictyostelium discoideum. Development 103:l-16. Wu L, Franke J (1990): A developmentally regulated and cAMP repressible gene of Dictyosteliun discoideum: Cloning and expression of the cyclic nucleotide phosphodiesterase inhibitor gene. Gene in press.
Dictyostelium discoideum: A Simple Eukaryotic Microorganism With a Complex Network of Regulation DAPHNE D. BLUMBERG Department of Biological Sciences, University of Maryland, Baltimore
Key words: Development, differentiation, gene expression
Dictyostelium discoideum is a soil microorganism, which normally grows by ingesting bacteria [for a review of the life cycle see Loomis, 19751. Cell proliferation ceases when differentiation begins. Dictyostelium uses a number of well-characterized secreted factors to direct various aspects of its developmental cycle [reviewed in Williams, 19881. Here two groups, Whitbread et al. and Rathi et al., describe secreted factors which are produced by growing cells. The work of Whitbread et al. describes a putative growth factor which appears to function primarily to stimulate cell proliferation. By contrast, the factor described by Clark's group, pre-starvation factor, is continuously secreted by growing cells and is shown to induce the accumulation of certain proteins and mRNAs previously thought to be induced by starvation as Dictyostelium cells enter the developmental cycle. Although preliminary data suggests t h a t these factors are different further characterization will be necessary to determine if their activities are entirely distinct. The transition from growth to development is accompanied by a number of changes in gene expression [reviewed in Kessin, 19881. Singleton and his coworkers have described two different groups of growth phase genes, V genes and H genes. Both groups of genes are inactivated a t the onset of development by a reduction in their transcription rate [Singleton et al., 19871. Here their structure, expression, and regulation is reviewed. Interestingly, two of the V genes are demonstrated to encode ribosomal proteins. The regulation of ribosomal protein gene expression has been extensively studied by Steel and Jacobson [reviewed in Steel and Jacobson, 19881. Post-transcriptional controls, in particular, controls which regulate the translational activity of the ribosomal protein mRNAs, have been previously described by Steel and Jacobson. Here they extend these studies to define a sequence in the 5'-untranslated region of one of the ribosomal protein mRNAs which is responsible for its translational activity. Cyclic AMP orchestrates the developmental cycle in Dictyostelium. The cells secrete and use cAMP as a n
O 1991 WILEY-LISS, INC.
attractant during the aggregation stage to direct the chemotaxis of cells into multicellular mounds [reviewed in Devreotes, 19891. As the cells assemble into mounds cAMP is again used to induce the expression of many genes specific to the prespore and prestalk cells [reviewed in Blumberg et al., 19881. Finally, there is increasing evidence that cAMP may also direct the series of morphogenetic changes that shape the final fruiting body during the terminal stages of cellular differentiation [reviewed in Schaap, 19861. In order to carry out these diverse functions, developing cells express a family of cAMP receptors on their surfaces [see articles in this volume by Devreotes and Kimmell. These receptors detect cAMP in both pulsatile and continuous modes. The enzyme cyclic nucleotide phosphodiesterase and its glycoprotein inhibitor interact to regulate the levels of extracellular cAMP available to interact with receptor [reviewed in Kessin, 19881. The genes encoding both of these enzymes have been cloned by the Kessin laboratory [see Lacombe et al., 1986; Wu and Franke, 19901. Franke and coworkers review here the structure and expression of these two genes and provide insight to the complex nature of the developmental regulation of these genes. The developmental regulation of another important group of enzymes, the cysteine proteinases, is reviewed by North and Cotter. The mechanism by which cAMP regulates the expression of the prespore genes has been extensively studied (see Developmental Genetics, 1988, vol. 9, for a comprehensive review). It has been established that concomitant protein synthesis is required for cAMP mediated gene expression [see Mehdy et al., 19831. Here Ratner and coworkers [Benedict et al.] demonstrate that transcription of these genes requires protein synthesis. The cAMP regulated prespore genes were initially studied a s a group of coordinately regu-
Received for publication July 31, 1990 Address reprint requests to Daphne D. Blumberg, Dept. of Biological Science, Univ. of Maryland, Baltimore, MD 21228.
64
BLUMBERG
lated mRNAs defined by genomic and cDNA clones [see Chung et al., 1981; Mehdy et al., 1983; Barklis and Lodish, 1983; Chisholm et al., 1984; Oyama and Blumberg, 19861. What was lacking was a knowledge of the developmental function of the protein products of these genes. Here Fosnaught and Loomis show that three of the genes which encode spore coat proteins are among this group of cAMP regulated prespore genes. The culmination of the developmental cycle results in a sorocarp of spore cells held atop a slender shaft of stalk cells. Under appropriate conditions the spore will germinate. Ennis’s group has identified and cloned a number of genes expressed at specific stages of spore germination [reviewed in Ennis et al., 19881.Here they describe a very unusual family of germination specific genes. These genes encode proteins which contain a long internal tetrapeptide repeat that is conserved among all of the genes in the group but otherwise the proteins share no other homology. The papers in this section clearly demonstrate the broad spectrum of regulatory phenomena that are involved in guiding this very simple eukaryotic microorganism through its distinct phases of growth, starvation, aggregation, differentiation, and finally the germination of the spores to restart the whole cycle.
REFERENCES Barklis E, Lodish HF (1983):Regulation of Dictyostelium discoideum mRNAs specific for prespore and prestalk cells. Cell 32:1139-1148. Blumberg DD, Comer, JF Higinbotham, KG (1988): A Ca2+ dependent signal transduction system participates in coupling expression of some CAMP-dependent prespore genes to the cell surface receptor. Dev Genet 9:359-369.
Chisholm RL, Barklis E, Lodish HF (1984): Mechanism of sequential induction of cell-type specific mRNAs in Dictyostelium discoideum. Nature 310:67-69. Chung S,Landfear SM, Blumberg DD, Cohen NS, Lodish HF (1981): Synthesis and stability of developmentally regulated Dictyostelium mRNAs are affected by cell-cell contact and CAMP. Cell 24:785797. Devreotes P (1989): Dictyostelium discoideum: A model system for cell-cell interactions in development. Science 245:1054-1058. Ennis HL, Giorda R, Ohmachi T, Shaw DR (1988):Characterization of genes that are developmentally regulated during Dictyostelzum spore germination. Dev Genet 9:303-313. Kessin RH (1988): Genetics of early Dictyostelium dzscoideum development. Microbiol Rev 52:29-49. Lacombe ML, Podgorski GJ, Franke J, Kesssin RH (1986): Molecular cloning and developmental expression of the cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum. J Biol Chem 261: 16811-16817. Loomis WF (1975):“Dictyostelzum discoideum: A Developmental System.” New York Academic press. Mehdy MC, Ratner D, Firtel RA (1983): Induction and modulation of cell type specific gene expression in Dictyostelium. Cell 32:763-771. Oyama M, Blumberg DD (1986): Changes during differentiation in requirements for cAMP for expression of cell type specific mRNA accumulation in Dzctyostelium discoideum. Dev Biol 117550-556. Schaap P (1986): Regulation of size and pattern in the cellular slime molds. Differentiation 33:l-16. Singleton CK, Delude RL, McPherson CE (1987): Characterization of genes which are deactivated upon the onset of development in Dictyostelium discozdeum. Dew Biol 119t433-441. Steel LF, Jacobson A (1988): Post-transcriptional regulation of ribosomal protein gene expression during development in Dictyosteliun discoideum. Dev Genet 9:421-434. Williams J G (1988):The role of diffusible molecules in regulating the cellular differentiation of Dictyostelium discoideum. Development 103:l-16. Wu L, Franke J (1990): A developmentally regulated and cAMP repressible gene of Dictyosteliun discoideum: Cloning and expression of the cyclic nucleotide phosphodiesterase inhibitor gene. Gene in press.
