title: Geminin is required for epithelial to mesenchymal transition at gastrulation.
abstract: Geminin is a multifunctional protein previously suggested to both maintain the bone morphogenetic protein inhibition required for neural induction and to control cell-cycle progression and cell fate in the early embryo. Since Geminin is required in the blastocyst on E3.5, we employed shRNA to examine its role during postimplantation development. Geminin knockdown inhibited the epithelial to mesenchymal transition (EMT) required at gastrulation and neural crest delamination, resulting in anterior-posterior axis and patterning defects, while overexpression promoted EMT at both locations. Geminin was negatively correlated with expression of E-cadherin, which is critically involved in controlling epithelial architecture. In addition, Geminin expression level was correlated with Wnt signaling and expression of the Wnt target gene Axin2 and with Msx2, and negatively correlated with the expression of Bmp4 and Neurog1 in quantitative reverse transcriptase-polymerase chain reaction analysis of RNAs from individual embryos. These results suggest that in addition to patterning the early embryo, Geminin plays a previously unrecognized role in EMT via its ability to affect Wnt signaling and E-cadherin expression.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Lisa S D
authors.initials: LS
authors.lastname: Emmett
authors.forename: K Sue
authors.initials: KS
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D054262:Gastrulation; D064248:Geminin; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway
chemical_list: D060466:Axin Protein; D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D015820:Cadherins; D018797:Cell Cycle Proteins; D064248:Geminin; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C111729:Axin2 protein, mouse; C525810:Bmp4 protein, mouse; C577997:Gmnn protein, mouse; C084119:MSX2 protein; C486336:Neurog1 protein, mouse