Wnt gene loss in flatworms

Abstract

Wnt genes encode secreted glycoproteins that act in cell-cell signalling to regulate a wide array of developmental processes, ranging from cellular differentiation to axial patterning. Discovery that canonical Wnt/β-catenin signalling is responsible for regulating head/tail specification in planarian regeneration has recently highlighted their importance in flatworm (phylum Platyhelminthes) development, but examination of their roles in the complex development of the diverse parasitic groups has yet to be conducted. Here, we characterise Wnt genes in the model tapeworm Hymenolepis microstoma and mine genomic resources of free-living and parasitic species for the presence of Wnts and downstream signalling components. We identify orthologs through a combination of BLAST and phylogenetic analyses, showing that flatworms have a highly reduced and dispersed complement that includes orthologs of only five subfamilies (Wnt1, Wnt2, Wnt4, Wnt5 and Wnt11) and fewer paralogs in parasitic flatworms (5-6) than in planarians (9). All major signalling components are identified, including antagonists and receptors, and key binding domains are intact, indicating that the canonical (Wnt/β-catenin) and non-canonical (planar cell polarity and Wnt/Ca(2+)) pathways are functional. RNA-Seq data show expression of all Hymenolepis Wnts and most downstream components in adults and larvae with the notable exceptions of wnt1, expressed only in adults, and wnt2 expressed only in larvae. The distribution of Wnt subfamilies in animals corroborates the idea that the last common ancestor of the Cnidaria and Bilateria possessed all contemporary Wnts and highlights the extent of gene loss in flatworms.

The Evolution of the Wnt Pathway

“…This indicates that basal protostomes also had an almost complete set of Wnt genes (Cho et al 2010). Other annelids and mollusks have lost several Wnt gene subfamilies, that is, Wnt8, -9, and -A in Helobdella robusta or Wnt4, -5, -6, -7, -8, -9, -11, and -16 in Patella vulgata (Prud'homme et al 2002;Cho et al 2010;Janssen et al 2010;Riddiford and Olson 2011). The Wnt genes of P. dumerilii show blastoporal and posterior expression in the growth zone (segment addition zone) of trochophoran larvae, and at the posterior side of each segment (Janssen et al 2010), reminiscent to arthropods (see below).…”

“…Their shape is similar to cnidarian planulae, but they have an elaborated gut with one pharyngeal opening derived from the blastopore. A survey of Wnt genes in platyhelminths, including Schmidtea mediterranea (turbellarian planarian), the parasitic Schistosoma mansoni (cestode), Echinococcus granulosis (trematode), and Hymenolepis microstoma (trematode) revealed a strong tendency toward gene loss (Riddiford and Olson 2011). Planarians possess nine Wnt genes, classified as members of the Wnt1, -2, -5, and -11 subfamilies, with putative gene duplications in the Wnt11 group (Gurley et al 2010;Riddiford and Olson 2011).…”

“…A survey of Wnt genes in platyhelminths, including Schmidtea mediterranea (turbellarian planarian), the parasitic Schistosoma mansoni (cestode), Echinococcus granulosis (trematode), and Hymenolepis microstoma (trematode) revealed a strong tendency toward gene loss (Riddiford and Olson 2011). Planarians possess nine Wnt genes, classified as members of the Wnt1, -2, -5, and -11 subfamilies, with putative gene duplications in the Wnt11 group (Gurley et al 2010;Riddiford and Olson 2011). Because most platyhelminths are highly diverged, it will be essential for future studies to unravel the Wnt gene repertoire of acoel flatworms, the putative bilaterian stem group.…”

Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain

“…We find that the secreted Wnt inhibitor notum (Petersen and Reddien, 2011) is expressed in anterior brain neurons and promotes brain size in regeneration, remodeling and homeostasis. notum (RNAi) brain phenotypes are suppressed by inhibition of wnt11-6/ wntA/wnt4a (Gurley et al, 2010;Kobayashi et al, 2007;Riddiford and Olson, 2011), hereafter referred to as wnt11-6, an inhibitor of brain size expressed in the posterior brain (Adell et al, 2009;Kobayashi et al, 2007). wnt11-6 signaling through beta-catenin-1 is required for notum expression in the brain, but is likely to inhibit brain size through β-catenin-independent signaling.…”

Increased taxon sampling reveals thousands of hidden orthologs in flatworms

“…Gene loss and orphan genes have been attributed to evolutionary changes leading to Platyhelminthes morphology (Berriman et al 2009;Martín-Durán and Romero 2011;Riddiford and Olson 2011;Tsai et al 2013;Breugelmans et al 2015). A prime example is the loss of centrosomes in planarian flatworms, where the apparent absence of genes critical to the functioning of animal centrosomes was used as evidence supporting the secondary loss of these organelles in Platyhelminthes (Azimzadeh et al 2012).…”