Experimental and evolutionary reconstruction of developmental signalling pathways

Research

 Dictyostelid social amoebas aggregate to form fruiting structures in response to starvation. This alternation between uni- and multicellular life styles offers unique opportunities to understand how multicellularity evolved and became increasingly more complex. Novel morphological features in multicellular organisms arise through changes in the developmental programmes that shape these features. These programmes are controlled by signals that are produced in a time- and space-dependent manner by the developing cells. cAMP is the most deeply conserved signal molecule in living organisms. It mediates the regulation of metabolism and motility by environmental stimuli in bacteria and the action of hormones in humans. In Dictyostelium discoideum, intracellular cAMP triggers the initiation of development and the maturation of spores and stalk cells in fruiting bodies. Extracellular cAMP acts as a chemoattractant to mediate aggregation of starving cells, and as a developmental signal to trigger the differentiation of prespore cells.

We use an experimental approach to understand how cAMP is produced in a time- and space dependent manner to exert these diverse functions, and how the cAMP signal is processed to alter gene expression patterns. In addition we use a comparative approach to understand how cAMP signalling pathways evolved in the Dictyostelids and how modifications in the component genes generated phenotypic complexity during Dictyostelid evolution. Our recent research shows that the role of intracellular cAMP in initiation of development and maturation of spores is evolutionary derived from a role in mediating drought-induced encystation of solitary amoebas. The role of secreted cAMP in coordinating aggregation of younger species, such as D.discoideum is evolutionary derived from a universal role in controlling fruiting body morphogenesis in all species. We recently showed that an early role of secreted cAMP was also to direct aggregated cells to form spores and not cysts in multicellular fruiting bodies.

We collaborate with Dr. Gloeckner of Berlin University to fully sequence and assemble the genomes of the species Dictyostelium lacteum, Polysphondylium pallidum and Dictyostelium fasciculatum. Together with the sequenced genome of D.discoideum, these species represent the 4 major groups of social amoebas and 1 billion years of multicellular evolution. The genome information will give us precedented potential to unravel how the mechanisms that generate shape and function in multicellular organisms came into being.

Publications

 Schaap, P. (2011) Evolution of developmental cyclic adenosine monophosphate signaling in the Dictyostelia from an amoebozoan stress response. Dev Growth Differ. 2011 May; 53(4):452-462.
 

Schaap, P., (2011) Evolutionary crossroads in developmental biology:  Dictyostelium discoideum. Development. 138(3), 387-396.

Kawabe, Y., Morio, T., James, J.L., Prescott, A.R., Tanaka, Y. and Schaap, P. (2009) Activated cAMP receptors turn encystation into sporulation. Proc. Nat. Acad. Sci. USA, 106, 7089-7094.

Ritchie, A.V., Van Es, S., Fouquet, C. and Schaap, P. (2008). From drought sensing to developmental control: evolution of cyclic AMP signaling in social amoebas. Mol. Biol. Evol. 25, 1-10.

Alvarez-Curto, E., Saran, S., Meima, M., Zobel, J., Scott, C., and Schaap, P. (2007) cAMP production by adenylyl cyclase G induces prespore differentiation in Dictyostelium slugs. Development 134, 959-966.

Schaap, P., Winckler, T., Nelson, M., Alvarez-Curto, E., Elgie, B., Hagiwara, H., Cavender, J., Milano-Curto, A., Rozen, D.E., Dingermann, T., Mutzel, R. and Baldauf, S.L. (2006) Molecular phylogeny and evolution of morphology in the social amoebas. Science 314, 661-663.

Alvarez-Curto, E., Rozen, D.E., Ritchie, A.V., Fouquet, C., Baldauf, S.L. and Schaap, P. (2005) Evolutionary origin of cAMP-based chemoattraction in the social amoebae. Proc. Natl. Acad. Sci. USA 102, 6385-6390.

Saran, S. and Schaap, P. (2004) Adenylyl cyclase G is activated by an intramolecular osmosensor. Mol. Biol. Cell 15, 1479-1486.

Meima, M.E., Weening, K.E., and Schaap, P. (2003) A novel cAMP-stimulated cAMP phosphodiesterase in Dictyostelium discoideum. J.Biol. Chem. 278, 14356-14362.