Crumbs2 promotes cell ingression during the epithelial-to-mesenchymal transition at gastrulation

• Published in: Nature cell biology Vol. 18; no. 12; pp. 1281 - 1291
• Main Authors: Ramkumar, Nitya, Omelchenko, Tatiana, Silva-Gagliardi, Nancy F., McGlade, C. Jane, Wijnholds, Jan, Anderson, Kathryn V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2016; Nature Publishing Group
• Subjects: 631/136/2086; 631/136/2086/2127; 631/136/334/1874/345; Animals; Basement Membrane - metabolism; Biology; Cancer Research; Cell Biology; Cells; Cellular proteins; Cytological research; Developmental Biology; Embryonic development; Embryos; Epithelial-Mesenchymal Transition; Gastrulation; Gene expression; Genetic aspects; Germ Layers - cytology; Homeodomain Proteins - metabolism; Imaging, Three-Dimensional; In Situ Hybridization; Insects; Life Sciences; Mammals - embryology; Membrane Proteins - metabolism; Mesoderm - cytology; Mesoderm - metabolism; Mice; Morphology; Mutation - genetics; Nonmuscle Myosin Type IIB - metabolism; Primitive Streak - cytology; Properties; Proteins; Stem Cells; Transcription factors; New York; United States > US
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb3442

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. Ramkumar  et al.  demonstrate that Crumbs2 is required in the cells of the primitive streak to promote cell ingression during the epithelial-to-mesenchymal transition, and maintains the integrity of the epiblast.