The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching

• Published in: Scientific reports Vol. 7; no. 1; pp. 9540 - 17
• Main Authors: Hildebrand, Sebastian, Hultin, Sara, Subramani, Aravindh, Petropoulos, Sophie, Zhang, Yuanyuan, Cao, Xiaofang, Mpindi, John, Kalloniemi, Olli, Johansson, Staffan, Majumdar, Arindam, Lanner, Fredrik, Holmgren, Lars
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.08.2017; Nature Publishing Group
• Subjects: 13; 13/100; 13/106; 14; 14/19; 38; 42; 631/136/1660; 631/80; 64; 64/116; 64/60; 82; 96/1; 96/34; 96/63; Actin; Actin Cytoskeleton - metabolism; Adherens junctions; Animals; Blastocyst - cytology; Blastocyst - metabolism; Blastocysts; Cadherins - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell junctions; Cell Line; Contractility; E-cadherin; Embryos; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelium - metabolism; Filaments; Gene Expression; Gene Knockout Techniques; Hatching; Humanities and Social Sciences; Humans; Inactivation; Intercellular Junctions - metabolism; Kinases; Localization; Medicin och hälsovetenskap; Mice; mRNA; multidisciplinary; Multiprotein Complexes - metabolism; Myosin; Packing; Protein Binding; Proteins; Science; Science (multidisciplinary); Skin - cytology; Skin - metabolism; Stress, Mechanical; Trophectoderm; Zebrafish; Zona pellucida
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10102-w

Epithelial cells connect via cell-cell junctions to form sheets of cells with separate cellular compartments. These cellular connections are essential for the generation of cellular forms and shapes consistent with organ function. Tissue modulation is dependent on the fine-tuning of mechanical forces that are transmitted in part through the actin connection to E-cadherin as well as other components in the adherens junctions. In this report we show that p100 amotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells over multiple layers. Genetic inactivation or depletion of amotL2 in epithelial cells in vitro or zebrafish and mouse in vivo , resulted in the loss of contractile actin filaments and perturbed epithelial packing geometry. We further showed that AMOTL2 mRNA and protein was expressed in the trophectoderm of human and mouse blastocysts. Genetic inactivation of amotL2 did not affect cellular differentiation but blocked hatching of the blastocysts from the zona pellucida. These results were mimicked by treatment with the myosin II inhibitor blebbistatin. We propose that the tension generated by the E-cadherin/AmotL2/actin filaments plays a crucial role in developmental processes such as epithelial geometrical packing as well as generation of forces required for blastocyst hatching.