title: Growth differentiation factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells.
abstract: BACKGROUND
  The central nervous system has a complex structural organization and consists of different subdomains along the antero-posterior axis. However, questions remain about the molecular mechanisms leading to the regionalization of this organ. We used a previously developed methodology to identify the novel patterning role of GDF11, a TGF-β signaling factor.
  
  
  RESULTS
  Using an assay based on neural differentiated mouse embryonic stem cells, GDF11 is shown to induce diencephalic (posterior forebrain), mesencephalic (midbrain) and metencephalic (anterior hindbrain) fates at the expense of telencephalic (anterior forebrain) specification. GDF11 has not previously been implicated in the early patterning of the nervous system. In addition, inhibition of the TGF-β type I receptors Alk4, Alk5 and Alk7 by the pharmacological inhibitor SB431542 caused a strong anteriorization of the cells.
  
  
  CONCLUSIONS
  Our findings suggest that GDF11 is involved in the earliest steps of the brain patterning during neurogenesis in the vertebrate embryo and is shown to be a regionalizing factor of the regional fate in the developing brain. This regionalization is not a typical posteriorizing signal as seen with retinoic acid, FGF or BMP molecules. To our knowledge, this is the first time that GDF11 is implicated in the earliest steps of the patterning of the neural plate.
authors.forename: Nele
authors.initials: N
authors.lastname: Vanbekbergen
authors.forename: Marijke
authors.initials: M
authors.lastname: Hendrickx
authors.affiliation: Department of Biology, Lab for Cell Genetics, Vrije Universiteit Brussel (VUB), 2 Pleinlaan, B-1050 Brussels, Belgium. lleyns@vub.ac.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Leyns
mesh_terms: D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D019521:Body Patterning / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055412:Growth Differentiation Factors / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D019485:Bone Morphogenetic Proteins; D004149:Dioxoles; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; C498933:Acvr1b protein, mouse; C515277:Acvr1c protein, mouse; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse