title: Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation.
abstract: During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior-posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3(-/-) embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.
authors.affiliation: Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany. jegea@neuro.mpg.de
authors.forename: Joaquim
authors.initials: J
authors.lastname: Egea
authors.forename: Christian
authors.initials: C
authors.lastname: Erlacher
authors.forename: Eloi
authors.initials: E
authors.lastname: Montanez
authors.forename: Ingo
authors.initials: I
authors.lastname: Burtscher
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Martin
authors.initials: M
authors.lastname: Hess
authors.forename: Falko
authors.initials: F
authors.lastname: Hampel
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Sanchez
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rodriguez-Manzaneque
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klein
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000473:pathology / Q000502:physiology; D019521:Body Patterning; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D047108:Embryonic Development; D004627:Embryonic Induction; D004707:Endoderm / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D015398:Signal Transduction
chemical_list: C514260:FLRT3 protein, mouse; D008562:Membrane Glycoproteins