The passage of an individual's genome to future generations is essential for the maintenance of species and is mediated by highly specialized cells, the germ cells. Genetic studies in a number of model organisms have provided insight into the molecular mechanisms that control specification, migration and survival of early germ cells. Focusing on Drosophila, we will discuss the mechanisms by which germ cells initially form and remain transcriptionally silent while somatic cells are transcriptionally active. We will further discuss three separate attractive and repellent guidance pathways, mediated by a G-protein coupled receptor, two lipid phosphate phosphohydrolases, and isoprenylation. We will compare and contrast these findings with those obtained in other organisms, in particular zebrafish and mice. While aspects of germ cell specification are strikingly different between these species, germ cell specific gene functions have been conserved. In particular, mechanisms that sense directional cues during germ cell migration seem to be shared between invertebrates and vertebrates.

hematopoiesis ͉ HOX genes ͉ microarray ͉ self-renewal ͉ embryoid bodies

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAr) provides attractive cues to Drosophila germ cells, guiding them toward the embryonic gonad. However, it remains unclear how HMGCoAr mediates this attraction. In a genomic analysis of the HMGCoAr pathway, we found that the fly genome lacks several enzymes required for cholesterol biosynthesis, ruling out cholesterol and cholesterol-derived proteins as mediators of PGC migration. Genetic analysis of the pathway revealed that two enzymes, farnesyl-diphosphate synthase and geranylgeranyl-diphosphate synthase, required for the production of isoprenoids, act downstream of HMGCoAr in germ cell migration. Consistent with a role in geranylgeranylation, embryos deficient in geranylgeranyl transferase type I show germ cell migration defects. Our data, together with similar findings in zebrafish, implicate an isoprenylated protein in germ cell attraction. The specificity and evolutionary conservation of the HMGCoAr pathway for germ cells suggest that an attractant common to invertebrates and vertebrates guides germ cells in early embryos.

Poly(dimethyl siloxane) elastomer, (PDMS) is widely used as a biomaterial. However, PDMS is very hydrophobic and easily colonized by several bacteria and yeasts. Consequently, surface modification has been used to improve its wettability and reduce bacterial adhesion. The aim of this work was to modify the PDMS surface in order to improve its hydrophilicity and bacterial cell repulsion to be used as a biomaterial. Plasma was used to activate the PDMS surface and sequentially promote the attachment of a synthetic surfactant, Pluronic F-68, or a polymer, Poly(ethylene glycol) methyl methacrylate, PEGMA. Bare PDMS, PDMS argon plasma activated, PDMS coated with Pluronic F-68 and PEGMA-grafted PDMS were characterized by contact angle measurements, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The influence of the surface modifications on blood compatibility of the materials was evaluated by thrombosis and haemolysis assays. The cytotoxicity of these materials was tested for mouse macrophages. After modification, AFM results suggest the presence of a distinct layer at the surface and by the contact angle measures it was observed an increase of hydrophilicity. XPS analysis indicates an increase of the oxygen content at the surface as a result of the modification. All the studied materials revealed no toxicity and were found to be non-haemolytic or in some cases slightly haemolytic. Therefore, plasma was found to be an effective technique for the PDMS surface modification.

The transcription factor Runx1 is a pivotal regulator of definitive hematopoiesis in mouse ontogeny. Vertebrate Runx1 is transcribed from 2 promoters, the distal P1 and proximal P2, which provide a paradigm of the complex transcriptional and translational control of Runx1 function. However, very little is known about the biologic relevance of alternative Runx1 promoter usage in definitive hematopoietic cell emergence. Here we report that both promoters are active at the very onset of definitive hematopoiesis, with a skewing toward the P2. Moreover, functional and morphologic analysis of a novel P1-null and an attenuated P2 mouse model revealed that although both promoters play important nonredundant roles in the emergence of definitive hematopoietic cells, the proximal P2 was most critically required for this. The nature of the observed phenotypes is indicative of a differential contribution of the P1 and P2 promoters to the control of overall Runx1 levels, where and when this is most critically required. In addition, the dynamic expression of P1-Runx1 and P2-Runx1 points at a requirement for Runx1 early in development, when the P2 is still the prevalent promoter in the emerging hemogenic endothelium and/or first committed hematopoietic cells. (Blood. 2010;115(15): 3042-3050) IntroductionThe generation of the definitive hematopoietic system during embryogenesis critically depends on the transcription factor Runx1. In mice, homozygous loss of Runx1 function results in embryonic lethality attributable to a complete lack of functional definitive hematopoietic stem cells (HSCs) and progenitor cells and hemorrhages in the central nervous system. 1-3 Runx1 belongs to the family of runt-domain transcription factors. The 3 mammalian members of this family, Runx1, 2, and 3, all are important developmental regulators and bind to the same DNA motif. 4 Although both Runx2 and Runx3 have been implicated in hematopoiesis, only Runx1 has a role in the emergence of definitive hematopoietic cells, 5 reflecting its specific expression at hemogenic sites. 6,7 Recently, it was shown that Runx1 is required in VE-cadherin ϩ cells of the embryo, within the developmental window that starts with the initiation of Runx1 expression in these cells and ends when/before definitive HSCs reach the embryonic day (E) 11 fetal liver (FL). 8 Although the precise developmental stage(s) at which Runx1 is required within this window remains to be determined, it is generally believed to be at the transition of hemogenic endothelium to definitive hematopoietic cells. 6,[8][9][10] In the adult, Runx1 is no longer critically required in HSCs, although it still plays important roles in maintaining hematopoietic homeostasis and in the generation of specific hematopoietic cells/lineages. [11][12][13] Not only the expression pattern of Runx1 but also its levels need to be tightly controlled for the normal emergence of HSCs in the embryo. 3 To gain insight into how this is achieved, we have initiated studies into the transcriptional regulation of Runx1. 14,15...

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This paper explores transformations in institutional norms about same-sex sexualities across four European countries: Bulgaria, Norway, Portugal and the UK. Focusing on the period from the late 1960s to the present day, it examines both endogenous, path-dependent nationally specific factors at work in the changing regulation of same-sex sexualities, particularly the campaigns of lesbian and gay movements, and exogenous influences exerted by processes of Europeanization and transnationalization. Three processes of normative change are discussed: the legitimation of same-sex sexual practice; the protection of lesbian, gay and bisexual (LGB) people; and the recognition of intimate relationships. We argue that there has been a radical shift in the landscape of heteronormativity in Europe, with the emergence of a new European norm of "homotolerance" and the progressive normalization of same-sex sexualities: a process of "homonormalization".

It has long been known that Hox genes are central players in patterning the vertebrate axial skeleton. Extensive genetic studies in the mouse have revealed that the combinatorial activity of Hox genes along the anterior-posterior body axis specifies different vertebral identities. In addition, Hox genes were instrumental for the evolutionary diversification of the vertebrate body plan. In this review, we focus on fundamental questions regarding the intricate mechanisms controlling Hox gene activity. In particular, we discuss the functional relevance of the precise timing of Hox gene activation in the embryo. Moreover, we provide insight into the epigenetic regulatory mechanisms that are likely to control this process and are responsible for the maintenance of spatially restricted Hox expression domains throughout embryonic development. We also analyze how specific features of each Hox protein may contribute to the functional diversity of Hox family. Altogether, the work reviewed here further supports the notion that the Hox program is far more complex than initially assumed. Exciting new findings will surely emerge in the years ahead. Developmental Dynamics 243:24-36,