Evolution of developmental signalling in Dictyostelid social amoebas

Abstract

Dictyostelia represent a tractable system to resolve the evolution of cell-type specialization, with some taxa differentiating into spores only, and other taxa with additionally one or up to four somatic cell types. One of the latter forms, Dictyostelium discoideum, is a popular model system for cell biology and developmental biology with key signalling pathways controlling cell-specialization being resolved recently. For the most dominant pathways, evolutionary origins were retraced to a stress response in the unicellular ancestor, while modifications in the ancestral pathway were associated with acquisition of multicellular complexity. This review summarizes our current understanding of developmental signalling in D. discoideum and its evolution.

Figure 1

Developmental signalling during the D. discoideum life cycle. During their 24 h life cycle, starving amoebas aggregate by secreting and relaying cAMP pulses to form multicellular mounds. The mound tip continues to emit cAMP pulses attracting cells from underneath, which push the tip upwards to form a slug. In the slug cells differentiate into precursors of spore and stalk, basal disc and upper and lower cup cells. Upon initiation of fruiting body formation, tip cells differentiate into stalk cells and move downwards. Most remaining cells move up the stalk and differentiate into spores and upper and lower cup cells. Cells that remain on the substratum differentiate into a basal disc. Stalk and basal disc cells share a similar highly vacuolated phenotype with a cellulose wall, while spores have condensed cytosol and a three-layered cellulosic wall that is also protein-rich. The environmental and secreted signals that control these life cycle transitions and the differentiation of amoebas are shown in red, with processes regulated by cAMP highlighted in yellow. The enzymes that synthesize secreted signals are shown in green, while proteins and small molecules that mediate intracellular signal processing are shown in blue. Blue arrows and t-crosses denote stimulatory and inhibitory effects, respectively, while double blue arrows signify that the mode of action of the signal is unknown. Abbreviations: AcaA: adenylate cyclase A; AcgA: adenylate cyclase G; AcrA: adenylate cyclase R; cAMP: 3′-5′-cyclic adenosine monophosphate; CarA: cAMP receptor 1; c-di-GMP: 3′,5′-cyclic diguanylic acid; ChlA: flavin-dependent halogenase Chlorination A; CMF: conditioned medium factor; DgcA: diguanylate cyclase A; DhkA: histidine phosphatase A; DhkB: histidine kinase B; DhkC: histidine kinase C; DIF-1: differentiation inducing factor 1; DimB: transcription factor DIF-insensitive mutant A; DmtA: des-methyl-DIF-1 methyltransferase; DokA: osmosensing histidine phosphatase; GtaC: GATA-binding transcription factor C; MBPD: 4-methyl-5-pentylbenzene-1,3-diol; NH₃: ammonia; PKA: cAMP-dependent protein kinase; PSF: prestarvation factor; PufA: pumilio RNA binding protein; RegA: cAMP phosphodiesterase with response regulator; SDF-2: spore differentiation factor 2; StlA: polyketide synthase Steely A; StlB: polyketide synthase Steely B; Tgr: transmembrane, IPT, IG, E-set, repeat protein; YakA: DYRK family protein kinase.

Figure 2

Evolution of developmental signalling from a stress response. Dictyostelia are members of the mostly unicellular kingdom of Amoebozoa. They can be subdivided into two branches each containing two major groups [6]. Comparative analysis of cAMP and DIF-1 signalling across the phylogeny suggests a scenario for the evolution of developmental signalling. cAMP was first used as intermediate for stress-induced encystation in unicellular amoebozoa, with stress acting on sensor histidine phosphatases to inhibit RegA, causing cAMP produced by AcrA, to increase and activate PKA and thereby encystation [34•, 35]. During Dictyostelid evolution sensor histidine kinases and phosphatase acquired novel roles in sensing developmental signals that control timely spore and stalk maturation. Early aggregating prototypes use secreted cAMP accumulating in aggregates as a signal for spore formation [39]. In early Dictyostelia, an emerging network of CarA, AcaA and PdsA produces cAMP pulses to coordinate fruiting body morphogenesis [38, 43]. Finally, group 4 acquires DIF-1 as a signal for basal disc formation, while addition of distal ‘early’ promoters to carA and acaA genes, and increased affinity of PdsA enables the use of cAMP as chemoattractant for aggregation in group 4 [38, 43, 48].