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

Autor(es)

Schubert, Frank Richard ^[1] ; Sobreira, Debora Rodrigues ^[2] ; Janousek, Ricardo Guerreiro ^[2] ; Alvares, Lucia Elvira ^[2] ; Dietrich, Susanne ^[3]

Afiliação do(s) autor(es)

^[1] Univ Portsmouth, Inst Biomed & Biomol Sci, Sch Biol Sci, Portsmouth PO1 2DY, Hants - England

^[2] Univ Estadual Campinas, State Univ Campinas, Dept Histol & Embryol, BR-13083863 Campinas, SP - Brazil

^[3] Univ Portsmouth, Inst Biomed & Biomol Sci, Sch Pharm & Biomed Sci, Portsmouth PO1 2DT, Hants - England

• Tipo de documento: Artigo Científico
• Fonte: BMC Evolutionary Biology; v. 14, AUG 6 2014.
• Citações Web of Science: 8

Resumo

Background: Dacts are multi-domain adaptor proteins. They have been implicated in Wnt and Tgf beta 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 Tgf beta 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 Tgf beta 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 Tgf beta signaling. Our work provides the basis for future structural and functional studies aimed at unraveling intracellular regulatory networks. (AU)

• Processo FAPESP: 06/05892-3 - Estudo das funções dos genes da família Frodo/Dapper na embriogênese dos vertebrados
• Beneficiário: Lúcia Elvira Álvares
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores