TGFβ signaling in Tribolium: vertebrate-like components in a beetle

Abstract

The cytokines of the TGFbeta superfamily are highly conserved in evolution and elicit a diverse range of cellular responses in all metazoa. In Drosophila, the signaling pathways of the two TGFbeta subfamilies, Activins and Bone Morphogenetic Proteins (BMPs), have been well studied. To address the question of whether the findings from Drosophila are representative of insects in general, we analyzed the components of TGFbeta-signaling present in the genome of the beetle Tribolium castaneum. We were able to identify orthologs of the BMPs Decapentaplegic and Glass bottom boat, of the Activins Activinbeta and Dawdle, as well as orthologs of the less well-known ligands Myoglianin and Maverick, together with orthologs of all TGFbeta receptors and cytoplasmic signal transducers present in Drosophila. This indicates that the diversity of TGFbeta signaling components is generally well conserved between Drosophila and Tribolium. However, the genome of the beetle-and of the bee Apis mellifera-lacks an ortholog of the Drosophila BMP Screw but does contain a vertebrate-like BMP10 homolog which is not found in Drosophila. Concerning BMP inhibitors, Tribolium displays an even more vertebrate-like ensemble of components. We found two orthologs of the vertebrate DAN family, Dan and Gremlin, and show embryonic expression of a vertebrate-like BAMBI ortholog, all of which are absent in Drosophila. This suggests that Tribolium might have retained a more ancestral composition of TGFbeta signaling components and that TGFbeta signaling underwent considerable change in the Drosophila lineage. Tribolium is an excellent model to study the function of these ancestral signaling components in insects.

The Lophotrochozoan TGF-β signalling cassette - diversification and conservation in a key signalling pathway

“…When TGF-b ligands form a complex with representatives of both types of receptor, the intracellular kinase domains of the receptors are brought together and the Type I receptor is phosphorylated and activated (Massagué 1998). In humans, a total of seven Type I and five Type II receptors have been described, while Tribolium castaneum, Apis mellifera and D. melanogaster possess a total of five -three Type I, and 2 Type II (van der Zee et al, 2008). The serine/threonine kinase receptor complements of the Lophotrochozoa have previously been the subject of investigation, with those of C. gigas already described (Herpin 2005).…”

“…No wider DAN class genes can be found in schistosomes or in the rotifers A. vaga or B. plicatilis, and loss of portions of this class are prevalent in other species -D. melanogaster, for example, has no DAN class genes in its genome (van der Zee et al, 2008), and DANs sensu stricto have been lost across the Lophotrochozoa (Table 1). DANs sequester a variety of ligands, with specificity varying depending on the DAN protein examined.…”

“…The evolution of some elements of the cassette is less well understood, particularly those components that act to modulate signalling. The TGF-b signalling pathway has been well studied in traditional ecdysozoan (van der Zee et al, 2008) and deuterostome (Massagué et al, 2000) model systems such as Drosophila melanogaster and Mus musculus. The few attempts that have been made at categorizing elements of the lophotrochozoan TGF-b cassette have typically been limited to individual elements and/ or single species (for example, Herpin et al, 2005, Freitas et al, 2007, Kuo and Weisblat 2011.…”

“…These are vital for many aspects of development, including the correct specification of dorsoventral polarity, and have been catalogued in ecdysozoans and deuterostomes (Holley et al, 1995). It has been observed that ecdysozoans have less diversity in these protein classes than vertebrate models (van der Zee et al, 2008). Tolloid, a zinc metalloprotease, is capable of cleaving Chordin, hence rereleasing the trapped ligand, as well as cleaving other potential repressors of TGF-b signalling, such as proteoglycans (Scott et al, 1999).…”

“…Down-regulation can be performed by pseudoreceptors such as BMP and membrane bound inhibitor (BAMBI, also known as Nma), which compete with functional Type I receptors for ligand binding (Onichtchouk et al, 1998). The existence of these regulatory mechanisms has been noted in protostomes previously (van der Zee et al, 2008), but the degree to which these are conserved across the Bilateria is unknown, and the possibility that these regulatory mechanisms have diversified, changed in function or have been lost in some lineages is yet to be explored.…”