Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea.
The EGFR pathway is an essential signaling system in animals, whose core components are the epidermal growth factors (EGF ligands) and their trans-membrane tyrosine kinase receptors (EGFRs). Despite extensive knowledge in classical model organisms, little is known of the composition and function of the EGFR pathway in most animal lineages. Here, we have performed an extensive search for the presence of EGFRs and EGF ligands in representative species of most major animal clades, with special focus on the planarian Schmidtea mediterranea. With the exception of placozoans and cnidarians, we found that the EGFR pathway is potentially present in all other analyzed animal groups, and has experienced frequent independent expansions. We further characterized the expression domains of the EGFR/EGF identified in S. mediterranea, revealing a wide variety of patterns and localization in almost all planarian tissues. Finally, functional experiments suggest an interaction between one of the previously described receptors, Smed-egfr-5, and the newly found ligand Smed-egf-6. Our findings provide the most comprehensive overview to date of the EGFR pathway, and indicate that the last common metazoan ancestor had an initial complement of one EGFR and one putative EGF ligand, which was often expanded or lost during animal evolution.
Department of Genetics, Faculty of Biology, University of Barcelona and Institute of Biomedicine of the University of Barcelona (IBUB), Av. Diagonal 643, edifici Prevosti, planta 1, 08028 Barcelona, Catalunya, Spain.
Sara
S
Barberán
Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, 5008 Bergen, Norway.
José M
JM
Martín-Durán
Department of Genetics, Faculty of Biology, University of Barcelona and Institute of Biomedicine of the University of Barcelona (IBUB), Av. Diagonal 643, edifici Prevosti, planta 1, 08028 Barcelona, Catalunya, Spain.
Francesc
F
Cebrià
D000818:Animals; D005075:Biological Evolution; D016000:Cluster Analysis; D030541:Databases, Genetic; D066255:EGF Family of Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D016013:Likelihood Functions; D010802:Phylogeny; D010932:Planarians / Q000378:metabolism*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
D066255:EGF Family of Proteins; D012330:RNA, Double-Stranded; D066246:ErbB Receptors