Forces generated by cell intercalation tow epidermal sheets in mammalian tissue morphogenesis.
While gastrulation movements offer mechanistic paradigms for how collective cellular movements shape developing embryos, far less is known about coordinated cellular movements that occur later in development. Studying eyelid closure, we explore a case where an epithelium locally reshapes, expands, and moves over another epithelium. Live imaging, gene targeting, and cell-cycle inhibitors reveal that closure does not require overlying periderm, proliferation, or supracellular actin cable assembly. Laser ablation and quantitative analyses of tissue deformations further distinguish the mechanism from wound repair and dorsal closure. Rather, cell intercalations parallel to the tissue front locally compress it perpendicularly, pulling the surrounding epidermis along the closure axis. Functional analyses in vivo show that the mechanism requires localized myosin-IIA- and α5β1 integrin/fibronectin-mediated migration and E-cadherin downregulation likely stimulated by Wnt signaling. These studies uncover a mode of epithelial closure in which forces generated by cell intercalation are leveraged to tow the surrounding tissue.
Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Evan
E
Heller
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden 01307, Germany; BIOTEC, Technische Universität Dresden, Tatzberg 47/49, Dresden 01307, Germany.
K Vijay
KV
Kumar
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden 01307, Germany; BIOTEC, Technische Universität Dresden, Tatzberg 47/49, Dresden 01307, Germany.
Stephan W
SW
Grill
Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.
Elaine
E
Fuchs
D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005143:Eyelids / Q000196:embryology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D039081:Integrin alpha5beta1 / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway
D015820:Cadherins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA