title: Characterization of Danio rerio Nanog and functional comparison to Xenopus Vents.
abstract: Nanog is a homeodomain transcription factor associated with the acquisition of pluripotency. Genome analyses of lower and higher vertebrates revealed that the existence of Nanog is restricted to gnathostomata but absent from agnatha and invertebrates. To elucidate the function of Nanog in nonmammalia, we identified the Danio rerio ortholog of Nanog and characterized its role in gain and loss of function experiments. We found Nanog to be crucial for survival of early zebrafish embryos, because depletion of Nanog led to gastrulation defects with subsequent lethality. Mouse Nanog overexpression could rescue these defects. Vice versa, zebrafish Nanog was found to promote proliferation and to inhibit differentiation of mouse embryonic stem cells in the absence of leukemia inhibitory factor. These findings indicate functional conservation of Nanog from teleost fishes to mammals. However, Nanog was lost in the genome of the anurans Xenopus laevis and Xenopus tropicalis. Phylogenetic analysis revealed that deletion probably occurred in a common anuran ancestor along with chromosomal translocations. The closest homologs of Nanog in Xenopus are the Vent proteins. We, therefore, investigated whether the Xvent genes might substitute for Nanog function in Xenopus. Although we found some similarities in phenotypes after overexpression and in the regulation of several marker genes, Xvent1/2 and Nanog cannot substitute each other. Depletion of Nanog in zebrafish cannot be rescued by ectopic expression of Xvent, and Xvent depletion in Xenopus cannot be overcome by ectopic expression of zebrafish Nanog.
authors.affiliation: Institute of Biochemistry, University of Ulm, Ulm, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schuff
authors.forename: Doreen
authors.initials: D
authors.lastname: Siegel
authors.forename: Melanie
authors.initials: M
authors.lastname: Philipp
authors.forename: Karin
authors.initials: K
authors.lastname: Bundschu
authors.forename: Nicole
authors.initials: N
authors.lastname: Heymann
authors.forename: Cornelia
authors.initials: C
authors.lastname: Donow
authors.forename: Walter
authors.initials: W
authors.lastname: Knöchel
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D014644:Genetic Variation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D000071317:Nanog Homeobox Protein; D011485:Protein Binding / Q000187:drug effects; D013045:Species Specificity; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D000071317:Nanog Homeobox Protein; C572119:Nanog protein, zebrafish; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D004247:DNA