The immunological mechanisms that regulate abortion are largely unknown. Here, we found that a distinct subset of lymphocytes, V␣14 NKT cells expressing an invariant antigen receptor encoded by V␣14͞J␣281 and V␤7 segments, accumulated in the decidua during pregnancy and provoked abortion upon stimulation with ␣-galactosylceramide (␣-GalCer), a specific ligand for V␣14 NKT cells. The ␣-GalCer-mediated abortion was not observed in V␣14 NKT-, IFN-␥-, tumor necrosis factor ␣-, or perforin-knock-out mice and appeared to be due to the degeneration of embryonic trophoblasts mediated by the activated V␣14 NKT cells whose perforin-dependent killing and production of IFN-␥ and tumor necrosis factor ␣ were essential. The possible role of the decidual V␣14 NKT cells in the pathogenesis of abortion is discussed.

Epithelial cysts are one of the fundamental architectures for mammalian organogenesis. Although in vitro studies using cultured epithelial cells have revealed proteins required for cyst formation, the mechanisms that orchestrate the functions of these proteins in vivo remain to be clarified. We show that the targeted disruption of the mouse Par3 gene results in midgestational embryonic lethality with defective epicardial development. The epicardium is mainly derived from epicardial cysts and essential for cardiomyocyte proliferation during cardiac morphogenesis. PAR3-deficient epicardial progenitor (EPP) cells do not form cell cysts and show defects in the establishment of apical cortical domains, but not in basolateral domains. In PAR3-deficient EPP cells, the localizations of aPKC, PAR6␤ and ezrin to the apical cortical domains are disturbed. By contrast, ZO1 and ␣4/␤1 integrins normally localize to cell-cell junctions and basal domains, respectively. Our observations indicate that EPP cell cyst formation requires PAR3 to interpret the polarity cues from cell-cell and cell-extracellular matrix interactions so that each EPP cell establishes apical cortical domains. These results also provide a clear example of the proper organization of epithelial tissues through the regulation of individual cell polarity.

Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together. Although mammalian separase also functions in chromosome segregation, our understanding of this process in mammals is still incomplete. We generated separase knockout mice, reporting an essential function for mammalian separase. Separase-deficient mouse embryonic fibroblasts exhibited severely restrained increases in cell number, polyploid chromosomes, and amplified centrosomes. Chromosome spreads demonstrated that multiple chromosomes connected to a centromeric region. Live observation demonstrated that the chromosomes of separase-deficient cells condensed, but failed to segregate, although subsequent cytokinesis and chromosome decondensation proceeded normally. These results establish that mammalian separase is essential for the separation of centromeres, but not of the arm regions of chromosomes. Other cell cycle events, such as mitotic exit, DNA replication, and centrosome duplication appear to occur normally. We also demonstrated that heterozygous separase-deficient cells exhibited severely restrained increases in cell number with apparently normal mitosis in the absence of securin, which is an inhibitory partner of separase.

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