Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E-cadherin.
Trophectoderm epithelium formation, the first visible differentiation process during mouse embryonic development, is affected in embryos lacking the cell adhesion molecule E-cadherin. Here we analyze the developmental potential of such E-cadherin-negative embryos, focusing on the organization of cell junctions and the cytoskeleton. To do this we used antibodies directed against alpha-, beta-, or gamma-(plakoglobin)-catenin and junctional and cytoskeletal proteins including ZO-1 and occludin (tight junctions), desmoglein1 (desmosomes), connexin43 (gap junctions), and EndoA (cytokeratin intermediate filaments). Membrane localization of alpha- and beta-catenin, and ZO-1, as well as cortical actin filament organization were abnormal in E-cadherin-negative embryos, and the expression levels of alpha- and beta-catenin were dramatically reduced, all suggesting a regulatory role for E-cadherin in forming the cadherin-catenin complex. In contrast, the membrane localization of plakoglobin, occludin, desmoglein1, connexin43, and cytokeratin filaments appeared unaltered. The unusual morphogenesis in E-cadherin-negative embryos apparently reflects defects in the molecular architecture of a supermolecular assembly involving zonulae adherens, tight junctions, and cortical actin filament organization, although the individual structures still appeared normal in electron microscopical analysis.
Ohsugi
M
M
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Larue
L
L
Schwarz
H
H
Kemler
R
R
D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D046508:Culture Techniques; D003598:Cytoskeletal Proteins / Q000032:analysis; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D004622:Embryo, Mammalian / Q000737:chemistry; D005260:Female; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D062793:Occludin; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D011247:Pregnancy; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin; D051176:beta Catenin