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Evidence suggests that the specification of primordial germ cells (PGCs) in the mammalian embryo does not depend on maternal determinants. Rather, previous genetic analysis in the mouse has shown that bone morphogenetic protein 4 (Bmp4) is required for the formation of both PGCs and allantois. Bmp4 is expressed in both the trophoblast-derived extraembryonic ectoderm (ExE) and in the epiblast-derived extraembryonic mesoderm (ExM), in which the PGCs, allantois primordium, and angioblasts are first detected. We have shown that Bmp4 made in the ExE functions to induce precursors of PGCs and allantois in the adjacent epiblast, resulting in complete lack of both cell types in homozygous null mutants. However, the function of Bmp4 in the ExM is totally unknown. To address this question, we generated tetraploid (4N) chimeras by aggregating Bmp4 null ES cells with wild-type tetraploid embryos. In this combination, wild-type tetraploid cells contribute to the extraembryonic trophoblast and primitive endoderm lineages but are excluded from the epiblast and its derivatives, including the ExM. Our results clearly demonstrate that Bmp4 made in the ExM does not affect the establishment of either PGC or allantois lineages, but is required for PGC localization and survival and for the differentiation of the allantois. These findings suggest that Bmp4 expressed in epiblast-derived tissues plays vital roles in reproduction by regulating both the development of the germ line and the vascular connection between the embryo and the placenta.I n the mouse embryo, primordial germ cells (PGCs) are first detected at the head-fold stage as a cluster of about 45 alkaline phosphatase (AP)-expressing cells at the base of the allantois (1). These PGCs subsequently migrate into the endoderm that gives rise to the hindgut (2), distribute along the hindgut, and finally move through the dorsal mesentery into the genital ridges (reviewed in ref.3). Lineage analysis has shown that the PGCs are derived before gastrulation from a subpopulation of proximal epiblast cells adjacent to the trophoblast-derived extraembryonic ectoderm (ExE). Significantly, these precursors are not lineage restricted but have descendants in both the germ line and extraembryonic tissues, such as the allantois, yolk sac mesoderm, and amnion (1).Previous studies suggest that the specification of the mouse germ line does not involve, as in many other organisms, the inheritance of maternal determinants. Rather, it appears that interactions between the trophoblast-derived ExE and the adjacent epiblast first establish precursors that can give rise to both PGCs and extraembryonic mesoderm cells. A second process then allocates descendants of these cells to the different lineages (reviewed in ref.3). This model says nothing about whether the interactions induce the de novo expression of genes specifically required for PGC development, or whether they maintain in the PGCs expression of key factors permitting pluripotency that are normally lost in cells that differentiate into somatic ...

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In the Japanese general practice population, masked hypertension defined by HBPM may be associated with an increased risk for stroke events. Use of HBPM may improve the assessment of BP-related risks and identify new therapeutic interventions aimed at preventing cardiovascular disease events.