Cooperation of Nectin-1 and Nectin-3 Is Required for Maintenance of Epidermal Stratification and Proper Hair Shaft Formation in the Mouse

Nectins constitute a family of four cell adhesion molecules which are localized on cell membrane. Mutations in NECTIN-1 gene cause the human ectodermal dysplasia syndrome (CLPED1) manifesting severe defects in skin and its appendages. However, nectin-1 null mutant mice have only a mild defect in epidermal stratification suggesting compensation by other nectins. We have analysed the epidermal and hair phenotypes of nectin-1; nectin-3 compound mutants. Epidermis was fragile and displayed severe defects in stratification, hair follicles were hypoplastic, and hair shaft structure was abnormal. Immunohistochemical analysis revealed severe defects in cell-cell junctions including adherens and tight junctions as well as desmosomes. It is therefore likely that the phenotypes were caused by impaired cell adhesion. The expression patterns of nectin-1 and nectin-3 together with the phenotypes in compound mutants indicated that heterophilic interactions between the two nectins are required for proper formation of epidermis and hair in mice. The nectin-1; nectin-3 compound mutant mice partially reproduced the phenotype of human CLPED1 patients.

The Dormancy Marker DRM1/ARP Associated with Dormancy but a Broader Role In Planta

Plants must carefully regulate their development in order to survive a wide range of conditions. Of particular importance to this is dormancy release, deciding when to grow and when not to, given these varying conditions. In order to better understand the growth release mechanism of dormant tissue at the molecular and physiological levels, molecular markers can be used. One gene family that has a long association with dormancy, which is routinely used as a marker for dormancy release, is DRM1/ARP (dormancy-associated gene-1/auxin-repressed protein). This plant-specific gene family has high sequence identity at the protein level throughout several plant species, but its function in planta remains undetermined. This review brings together and critically analyzes findings on the DRM1/ARP family from a number of species. We focus on the relevance of this gene as a molecular marker for dormancy, raising questions of what its role might actually be in the plant.

Actin Colocalization with Metaphase Chromosomes of the Second Meiosis in Ovulated Mouse Oocytes

Functional interrelation of nuclear actin with transcriptional active chromatin in the interphase nucleus was reliably established in numerous experiments, but the relationship between actin and transcriptional silent chromatin is still unclear. We examined localization area of the second meiotic division metaphase plate in ovulated mouse oocytes with the aim to study the possibility of actin-chromatin colocalization and uncovering the distribution patterns of different functional forms of actin near the metaphase chromosomes. Confocal microscopy and probes for actin that are distinguished from each other by the mechanism of actin binding (TRITC-phalloidin, fluorescent DNase-I, and antibodies against fragment of C-terminal and fragment of N-terminal domain of actin) were used for actin visualization. Despite the fact that TRITC-phalloidin could not detect F-actin in the area of metaphase plate, oocytes staining with antibody against fragment of the actin N-terminal domain demonstrates the presence near the metaphase chromosomes of some spindle-like structure composed of actin filaments. Among all used probes for actin, only the antibody against fragment of the C-terminal domain detected accurate actin colocalization with metaphase chromosomes. We conclude that this antibody labeled noncanonical form of the nuclear actin existing in long-term association with highly condensed chromatin.

Targeted Disruption of Calcium/NFAT Signaling Reveals a Left-Right Determination Disorder in the Pharyngeal Arch Artery

An immunosuppressant was injected into pregnant mice in order to investigate whether the immune response is involved in differentiation during embryonic development. Injection of 3 mg/kg of FK506, an inhibitor of calcineurin, early in the organogenesis period increased the penetrance of right aortic arch formation by 32% compared with saline injection. Immunosuppressants such as FTY720 and rapamycin did not affect left/right (L/R) determination. FK506 is known to work by restricting NFAT (nuclear factor activated T-cell) dephosphorylation. An L/R determination disorder in cardiac outflows appeared when an NFATc4 siRNA was directly injected into the amniotic fluid. As for the mechanism, Pitx2, which is normally expressed on the left-hand side, was found to be expressed also on the right-hand side. Furthermore, it turned out that administration of FK506 also prevented the dephosphorylation of NSFL1 cofactor p47. When an siRNA targeting p47 was introduced into the amniotic fluid of FK506-treated fetuses, both of the dorsal arteries—which should normally become one—remained. These findings indicate that the mother's immune system contributes not only to self defense, but also to remodeling processes in fetal morphogenesis.