RealTimeChess: Lessons from a Participatory Design Process for a Collaborative Multi-Touch, Multi-User Game

We report on a long-term participatory design process during which we designed and improved RealTimeChess, a collaborative but competitive game that is played using touch input by multiple people on a tabletop display. During the design process we integrated concurrent input from all players and pace control, allowing us to steer the interaction along a continuum between high-paced simultaneous and low-paced turn-based gameplay. In addition, we integrated tutorials for teaching interaction techniques, mechanisms to control territoriality, remote interaction, and alert feedback. Integrating these mechanism during the participatory design process allowed us to examine their effects in detail, revealing for instance effects of the competitive setting on the perception of awareness as well as territoriality. More generally, the resulting application provided us with a testbed to study interaction on shared tabletop surfaces and yielded insights important for other time-critical or attention-demanding applications.

RSPO1/beta-Catenin Signaling Pathway Regulates Oogonia Differentiation and Entry into Meiosis in the Mouse Fetal Ovary

Differentiation of germ cells into male gonocytes or female oocytes is a central event in sexual reproduction. Proliferation and differentiation of fetal germ cells depend on the sex of the embryo. In male mouse embryos, germ cell proliferation is regulated by the RNA helicase Mouse Vasa homolog gene and factors synthesized by the somatic Sertoli cells promote gonocyte differentiation. In the female, ovarian differentiation requires activation of the WNT/β-catenin signaling pathway in the somatic cells by the secreted protein RSPO1. Using mouse models, we now show that Rspo1 also activates the WNT/β-catenin signaling pathway in germ cells. In XX Rspo1(−/−) gonads, germ cell proliferation, expression of the early meiotic marker Stra8, and entry into meiosis are all impaired. In these gonads, impaired entry into meiosis and germ cell sex reversal occur prior to detectable Sertoli cell differentiation, suggesting that β-catenin signaling acts within the germ cells to promote oogonial differentiation and entry into meiosis. Our results demonstrate that RSPO1/β-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm

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The sex of an individual is determined by the fate of the gonad. This organ arises from two different structures: the coelomic epithelium and a mesenchymal part that forms from the mesonephros. The early embryonic gonad can differentiate into a testis or an ovary, thus suggesting that at an early stage the gonad is bipotential. Testis formation requires differentiation of Sertoli cells, which will form the supporting cell lineage of the seminiferous tubules. These cells synthesize Anti-Mullerian Hormone (AMH), which induces regression of the Mullerian duct, thus counteracting the development of female internal genitalia. Moreover, Sertoli cells favor recruitment of other somatic cell lineages migrating from the mesonephros that are also crucial for testis development to occur. The interstitial area of the testis contains the steroidogenic cells (Leydig cells), which have the function of producing androgens. These hormones stimulate the differentiation of internal and external genitalia of the male [for a review see Gonad differentiation depends on the paternal transmission of the sex chromosome. Thus, an XY embryo develops as a male, whereas an XX embryo becomes female. Most of the genes involved in this developmental pathway have been discovered from genetic studies of human XY sex-reversal. At a molecular level, the Y chromosome encodes a testis determining factor, SRY [Sinclair et al., Key Words Abstract In mammals, the sex of the embryo is determined during development by its commitment either to the male or female genetic program regulating testicular or ovarian organogenesis. Major steps towards unraveling sex determination in mammals are achieved by the identification of key genes involved in human pathologies and the application of mouse genetics to analyze their function. While the expression of Sry and Sox9 is sufficient to induce the male developmental program, the molecular pathways that specify ovarian differentiation were unclear before the recent demonstration that mutations in the RSPO1 gene induce femaleto-male sex reversal in XX patients. By generating the corresponding mouse model, we have shown that Rspo1 is so far the earliest known gene controlling the female genetic developmental program. Rspo1 activates the canonical ␤ -catenin signaling pathway required for female somatic cell differentiation and germ cell commitment into meiosis. The aim of this review is to describe the roles of R-spondins (Rspo) in developmental processes and disorders and the current knowledge obtained from murine models. A particular focus will be on Rspo1 and its crucial function in sex determination

Transient development of ovotestes in XX Sox9 transgenic mice

AbstractThe sex of an individual results from the paternal transmission of the SRY gene located on the Y chromosome. In turn, SRY initiates Sox9 expression, a transcription factor required for testicular differentiation. Ectopic activation of SOX9 in XX Wt1:Sox9 transgenic mice induces female-to-male sex reversal in adult mice. Here we show that complete sex reversal is preceded by a transient phase of ovotestis differentiation with XX Wt1:Sox9 transgenic gonads containing a testicular central region and one or both ovarian poles indicating that Wt1:Sox9 is not as efficient as Sry to induce male development. In XX Wt1:Sox9Tg/+ gonads, transgenic Sox9 is expressed earlier than Sox9 in XY gonads and is able to induce the expression of EGFP, knocked into the 3′ UTR of Sox9 indicating that SOX9 is involved in the initiation and maintenance of its own expression. However, the delayed onset of expression of endogenous Sox9–EGFP suggests that this activation requires other factors, whose expression depends on SOX9. In the testicular regions of the XX Wt1:Sox9 ovotestes, proliferation of the XX fetal germ cells is hampered and they differentiate as pro-spermatogonia. This indicates that XX germ cells are not competent to respond to proliferative signals released from a testicular environment. In the ovarian regions, despite the continuous mRNA expression of the WT1:Sox9 transgene, the SOX9 protein does not accumulate suggesting that regulation of this gene in ovarian cells involves post-transcriptional mechanisms. Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth

Mobile DNA transposition in somatic cells

It had been long assumed that almost all insertions of mobile DNA elements occurred during germ-cell development rather than in somatic-cell development, but solid evidence for transposition in somatic cells is now accumulating. To add to this evidence, a recent paper in Mobile DNA reports the somatic transposition of a site-specific retrotransposon, R2, into its insertion site in 28S ribosomal DNA in Drosophila embryos

Crosstalk between androgen receptor and WNT/β-catenin signaling causes sex-specific adrenocortical hyperplasia in mice

Female bias is highly prevalent in conditions such as adrenal cortex hyperplasia and neoplasia, but the reasons behind this phenomenon are poorly understood. In this study, we show that overexpression of the secreted WNT agonist R-spondin 1 (RSPO1) leads to ectopic activation of WNT/β-catenin signaling and causes sex-specific adrenocortical hyperplasia in mice. Although female adrenals show ectopic proliferation, male adrenals display excessive immune system activation and cortical thinning. Using a combination of genetic manipulations and hormonal treatment, we show that gonadal androgens suppress ectopic proliferation in the adrenal cortex and determine the selective regulation of the WNT-related genes Axin2 and Wnt4. Notably, genetic removal of androgen receptor (AR) from adrenocortical cells restores the mitogenic effect of WNT/β-catenin signaling. This is the first demonstration that AR activity in the adrenal cortex determines susceptibility to canonical WNT signaling-induced hyperplasia.</p

Fgf9 and Wnt4 Act as Antagonistic Signals to Regulate Mammalian Sex Determination

The genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9) and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch— Sry in the case of mammals—is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways