title: Ventx factors function as Nanog-like guardians of developmental potential in Xenopus.
abstract: Vertebrate development requires progressive commitment of embryonic cells into specific lineages through a continuum of signals that play off differentiation versus multipotency. In mammals, Nanog is a key transcription factor that maintains cellular pluripotency by controlling competence to respond to differentiation cues. Nanog orthologs are known in most vertebrates examined to date, but absent from the Anuran amphibian Xenopus. Interestingly, in silico analyses and literature scanning reveal that basal vertebrate ventral homeobox (ventxs) and mammalian Nanog factors share extensive structural, evolutionary and functional properties. Here, we reassess the role of ventx activity in Xenopus laevis embryos and demonstrate that they play an unanticipated role as guardians of high developmental potential during early development. Joint over-expression of Xenopus ventx1.2 and ventx2.1-b (ventx1/2) counteracts lineage commitment towards both dorsal and ventral fates and prevents msx1-induced ventralization. Furthermore, ventx1/2 inactivation leads to down-regulation of the multipotency marker oct91 and to premature differentiation of blastula cells. Finally, supporting the key role of ventx1/2 in the control of developmental potential during development, mouse Nanog (mNanog) expression specifically rescues embryonic axis formation in ventx1/2 deficient embryos. We conclude that during Xenopus development ventx1/2 activity, reminiscent of that of Nanog in mammalian embryos, controls the switch of early embryonic cells from uncommitted to committed states.
authors.affiliation: Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Scerbo
authors.forename: Fabrice
authors.initials: F
authors.lastname: Girardot
authors.forename: Céline
authors.initials: C
authors.lastname: Vivien
authors.forename: Gabriel V
authors.initials: GV
authors.lastname: Markov
authors.forename: Guillaume
authors.initials: G
authors.lastname: Luxardi
authors.forename: Barbara
authors.initials: B
authors.lastname: Demeneix
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.forename: Laurent
authors.initials: L
authors.lastname: Coen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C497996:MSX1 protein, Xenopus; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D011994:Recombinant Proteins; D029867:Xenopus Proteins