title: Crumbs2 promotes cell ingression during the epithelial-to-mesenchymal transition at gastrulation.
abstract: During gastrulation of the mouse embryo, individual cells ingress in an apparently stochastic pattern during the epithelial-to-mesenchymal transition (EMT). Here we define a critical role of the apical protein Crumbs2 (CRB2) in the gastrulation EMT. Static and live imaging show that ingressing cells in Crumbs2 mutant embryos become trapped at the primitive streak, where they continue to express the epiblast transcription factor SOX2 and retain thin E-cadherin-containing connections to the epiblast surface that trap them at the streak. CRB2 is distributed in a complex anisotropic pattern on apical cell edges, and the level of CRB2 on a cell edge is inversely correlated with the level of myosin IIB. The data suggest that the distributions of CRB2 and myosin IIB define which cells will ingress, and we propose that cells with high apical CRB2 are basally extruded from the epiblast by neighbouring cells with high levels of apical myosin.
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Nitya
authors.initials: N
authors.lastname: Ramkumar
authors.affiliation: Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Omelchenko
authors.affiliation: The Hospital for Sick Children, Arthur and Sonia Labatt Brain Tumor Research Center and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Silva-Gagliardi
authors.affiliation: The Hospital for Sick Children, Arthur and Sonia Labatt Brain Tumor Research Center and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: C Jane
authors.initials: CJ
authors.lastname: McGlade
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Wijnholds
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Kathryn V
authors.identifier: http://orcid.org/0000-0003-1657-2161
authors.initials: KV
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D054262:Gastrulation; D005855:Germ Layers / Q000166:cytology; D018398:Homeodomain Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D017403:In Situ Hybridization; D008322:Mammals / Q000196:embryology; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D054240:Primitive Streak / Q000166:cytology*
chemical_list: C568885:Crb2 protein, mouse; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C484194:Meox2 protein, mouse; D024501:Nonmuscle Myosin Type IIB