Myoblast fusion takes place in two steps in mammals and in

During myogenesis in Drosophila embryos, a prominent adhesive structure is formed between precursor cells and fusion-competent myoblasts (fcms). Here, we show that Duf/Kirre and its interaction partners Rols7 (found in founder myoblasts and growing myotubes) and Sns (found in fcms) are organized in a ring-structure at the contact points of fcms with precursor cells, while cytoskeletal components like F-actin and Titin are centered in this ring in both cell types. The cytoplasmic protein Blow colocalizes with the actin plugs in fcms after cell adhesion. Furthermore, the requirement of additional as yet unidentified components was demonstrated by using mammalian C2C12 myoblasts. In this study, we propose that the fusion-restricted myogenic-adhesive structure (FuRMAS) is pivotal in linking cell adhesion as well as local F-actin assembly and dynamics to downstream events that ultimately lead to plasma membrane fusion. Moreover, we suggest that the FuRMAS may restrict the area of membrane breakdown. Developmental Dynamics 236:404 -415, 2007.

Robust cytotoxic CD8 + T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8 + T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4 −/− ) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenesspecific CD8 + T cells with impaired effector phenotype and function. Transfer of wild-type CD8 + T cells into Irf4 −/− mice improved bacterial clearance, suggesting an intrinsic defect of CD8 + T cells in Irf4 −/− mice. Following transfer into wild-type recipients, Irf4 −/− CD8 + T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4 −/− CD8 + T cells rescued the defect. During acute infection, Irf4 −/− CD8 + T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4 −/− CD8 + T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4 −/− CD8 + T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4 + T-cell differentiation, the identification of its decisive role in peripheral CD8 + T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.

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Folate intake during pregnancy may affect the regulation of DNA methylation during fetal development. The genomic regions in the offspring that may be sensitive to folate exposure during in utero development have not been characterized. Using genome-scale profiling, we investigated DNA methylation in 2 immune cell types (CD4(+) and antigen-presenting cells) isolated from neonatal cord blood, selected on the basis of in utero folate exposure. High-folate (HF; n=11) and low-folate (LF; n=12) groups were selected from opposite extremes of maternal serum folate levels measured in the last trimester of pregnancy. A comparison of these groups revealed differential methylation at 7 regions across the genome. By far, the biggest effect observed was hypomethylation of a 923 bp region 3 kb upstream of the ZFP57 transcript, a regulator of DNA methylation during development, observed in both cell types. Levels of H3/H4 acetylation at ZFP57 promoter and ZFP57 mRNA expression were higher in CD4(+) cells in the HF group relative to the LF group. Hypomethylation at this region was replicated in an independent sample set. These data suggest that exposure to folate has effects on the regulation of DNA methylation during fetal development, and this may be important for health and disease.