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First published online 19 October 2004
doi: 10.1242/jcs.01424

Journal of Cell Science 117, 5599-5608 (2004)
Published by The Company of Biologists 2004
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Research Article

Contribution of JAM-1 to epithelial differentiation and tight-junction biogenesis in the mouse preimplantation embryo

Fay C. Thomas1, Bhavwanti Sheth1, Judith J. Eckert1,2, Gianfranco Bazzoni3, Elisabetta Dejana3 and Tom P. Fleming1,*

1 School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK
2 Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Coxford Road, Southampton, SO16 5YA, UK
3 Laboratory of Vascular Biology, Istituto di Ricerche Farmacologiche, Mario Negri, 20157 Milano, Italy

* Author for correspondence (e-mail: tpf{at}soton.ac.uk)

Accepted 30 July 2004

We have investigated the contribution of the tight junction (TJ) transmembrane protein junction-adhesion-molecule 1 (JAM-1) to trophectoderm epithelial differentiation in the mouse embryo. JAM-1-encoding mRNA is expressed early from the embryonic genome and is detectable as protein from the eight-cell stage. Immunofluorescence confocal analysis of staged embryos and synchronized cell clusters revealed JAM-1 recruitment to cell contact sites occurred predominantly during the first hour after division to the eight-cell stage, earlier than any other TJ protein analysed to date in this model and before E-cadherin adhesion and cell polarization. During embryo compaction later in the fourth cell cycle, JAM-1 localized transiently yet precisely to the apical microvillous pole, where protein kinase C{zeta} (PKC{zeta}) and PKC{delta} are also found, indicating a role in cell surface reorganization and polarization. Subsequently, in morulae and blastocysts, JAM-1 is distributed ubiquitously at cell contact sites within the embryo but is concentrated within the trophectoderm apicolateral junctional complex, a pattern resembling that of E-cadherin and nectin-2. However, treatment of embryos with anti-JAM-1-neutralizing antibodies indicated that JAM-1 did not contribute to global embryo compaction and adhesion but rather regulated the timing of blastocoel cavity formation dependent upon establishment of the trophectoderm TJ paracellular seal.

Key words: Junction adhesion molecule, Tight junction, Trophectoderm epithelium, Cell polarity, Blastocyst, Adherens junction




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