Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of a regulatory module with putative implication in pancreas development.

Maria Kapasa,Stilianos Arhondakis,Sophia Kossida

doi:10.1186/1745-6150-5-49

Maria Kapasa, Stilianos Arhondakis + Show 1 more

Open Access

https://doi.org/10.1186/1745-6150-5-49

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Abstract

BackgroundWnt5 genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that Wnt5 gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two Wnt5 paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics.ResultsIn this study, the phylogeny of Wnt5 genes was investigated in species belonging to protostomia and deuterostomia. Furthermore, an in silico regulatory region analysis of Wnt5 paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the Wnt5 gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind.ConclusionsResults and observations presented in this study, allow us to conclude that during evolution, the Wnt5 gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the Wnt5 orthologs do not share the same function during pancreas development. As a final remark, we suggest that an in silico comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs.ReviewersThis article was reviewed by Sarath Janga (nominated by Sarah Teichmann), Ran Kafri (nominated by Yitzhak Pilpel), and Andrey Mironov (nominated by Mikhail Gelfand).

Highlights

Wnt5 genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes
Summarizing, the Wnt5a gene was surrounded by Erc2 and Cacna2d3, with Ltrm1 being in the genomic neighbourhood of the latter (Figure 2a)
The above findings suggest that a gene duplication event has occurred approximately at the divergence time of gnathostomata, involving the Wnt5 gene and its neighbouring genomic region, followed by genomic translocation

Summary

Introduction

Wnt genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes. A previous study [5] showed that in some species carrying both Wnt paralogs only one participates in cell migration events during the endocrine pancreas development. They showed that in early mice embryos Wnt5a expression guides the migration of islet cells in order to properly form the endocrine part of pancreas, while in zebrafish embryos, the Wnt signalling is required for the proper migration of insulin producing cells during pancreas development [5]. Previous studies aiming to establish the function of Wnt genes, observed that, despite the similarity in expression pattern between zebrafish ZfWnt and murine Wnt5a during pancreatic development [9,10,11,12], the former was found to be characterized by a higher amino acid sequence similarity to that of the mouse Wnt5b [3]

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