Dact genes are chordate specific regulators at the intersection of Wnt and Tgf-β signaling pathways

BMC Evolutionary Biology

Susanne Dietrich³  Lúcia Elvira Alvares²  Ricardo Guerreiro Janousek²  Débora Rodrigues Sobreira³  Frank Richard Schubert¹ 

[1] Institute of Biomedical and Biomolecular Sciences, School of Biological Sciences, University of Portsmouth, King Henry Building, King Henry I Street, Portsmouth PO1 2DY, UK;Department of Histology and Embryology, State University of Campinas - UNICAMP, Rua Charles Darwin, s/n°, CP 6109, Campinas, SP CEP 13083-863, Brazil;Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, St. Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK

关键词: Vertebrates;    Chordates;    Expression;    Protein motifs;    Evolution;    Tgfβ signaling;    Wnt signaling;    Frodo;    Dapper;    Dact;   

Others  :  1118040
DOI  :  10.1186/1471-2148-14-157

 received in 2013-10-06, accepted in 2014-07-04,  发布年份 2014

【 摘 要 】

Background

Dacts are multi-domain adaptor proteins. They have been implicated in Wnt and Tgfβ signaling and serve as a nodal point in regulating many cellular activities. Dact genes have so far only been identified in bony vertebrates. Also, the number of Dact genes in a given species, the number and roles of protein motifs and functional domains, and the overlap of gene expression domains are all not clear. To address these problems, we have taken an evolutionary approach, screening for Dact genes in the animal kingdom and establishing their phylogeny and the synteny of Dact loci. Furthermore, we performed a deep analysis of the various Dact protein motifs and compared the expression patterns of different Dacts.

Results

Our study identified previously not recognized dact genes and showed that they evolved late in the deuterostome lineage. In gnathostomes, four Dact genes were generated by the two rounds of whole genome duplication in the vertebrate ancestor, with Dact1/3 and Dact2/4, respectively, arising from the two genes generated during the first genome duplication. In actinopterygians, a further dact4r gene arose from retrotranscription. The third genome duplication in the teleost ancestor, and subsequent gene loss in most gnathostome lineages left extant species with a subset of Dact genes. The distribution of functional domains suggests that the ancestral Dact function lied with Wnt signaling, and a role in Tgfβ signaling may have emerged with the Dact2/4 ancestor. Motif reduction, in particular in Dact4, suggests that this protein may counteract the function of the other Dacts. Dact genes were expressed in both distinct and overlapping domains, suggesting possible combinatorial function.

Conclusions

The gnathostome Dact gene family comprises four members, derived from a chordate-specific ancestor. The ability to control Wnt signaling seems to be part of the ancestral repertoire of Dact functions, while the ability to inhibit Tgfβ signaling and to carry out specialized, ortholog-specific roles may have evolved later. The complement of Dact genes coexpressed in a tissue provides a complex way to fine-tune Wnt and Tgfβ signaling. Our work provides the basis for future structural and functional studies aimed at unraveling intracellular regulatory networks.

【 授权许可】

   
2014 Schubert et al.; licensee BioMed Central Ltd.

【 图 表 】

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