Lindsey Mork

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..In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways...

..Several sexually dimorphic phenotypes correlate with sex-chromosome dosage rather than with phenotypic sex. New research suggests that sex chromosome dimorphism helps to regulate gene silencing...

..Mechanisms of testis organogenesis triggered downstream of SRY include pathways of cell signaling controlling cell reorganization, cell proliferation, cell migration, and vascularization...

..The induction of cell migration represents the earliest signaling pathway yet assigned to Sry...

..More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates...

..We present evidence that normal morphological development of the fetal gonad occurs in both sexes in T. scripta after germ cell depletion, suggesting a conservation of developmental mechanisms across vertebrates...

..We also discuss the plasticity of the adult gonad and consider how different genetic and environmental conditions can induce transitions between testis and ovary morphology...

..This model of vascular development in an internal organ has a direct impact on the current dogma of vascular integration during organ development and presents important parallels with mechanisms of tumor vascularization...

..We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background...

..We suggest that at the stage when germ cells commit to meiosis, they reinforce ovarian fate by antagonizing the testis pathway...

..Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells...

..These findings add complexity to the standard model of sex determination in which the Sertoli and granulosa cells of the adult testis and ovary directly stem from the supporting cell precursors of the bipotential gonad...

..FGF9 is necessary for 11.5 dpc XY gonocyte survival and is the earliest reported factor with a sex-specific role in regulating germ cell survival...

..The identification of beta-catenin as a key pro-ovarian and anti-testis signaling molecule will further our understanding of the mechanisms controlling sex determination and the molecular mechanisms that lead to sex-reversal...

..The nuclear localization of FGFR2 coincides with the initiation of Sry expression and the nuclear localization of SOX9 during the early differentiation of Sertoli cells and the determination of male fate...

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..We show that germ cell clusters in the fetal gonad arise through aggregation as well as cell division. Intercellular bridges, however, are likely restricted to cells of the same genotype...

..This newly formed arterial system establishes a new pattern of blood flow in the XY gonad, which we speculate may have an important role in export of testosterone to masculinize the XY embryo...

..This suggests that either there is a function for the remaining N-terminal of GM114, or that there are alternative mechanisms in the mammalian system that control germ cell differentiation...

..The factors involved in this process remain to be identified...

..We conclude that typical testis architecture results from the maintenance and elaboration of primitive sex cords in T. scripta rather than the assembly of de novo structures as in mouse...

..We believe these studies suggest that proliferation is involved not only in the elaboration of organ pattern, but also in the choice between patterns (male and female) in the bipotential gonad...

..Thus, we propose that WNT4 acts through FST to regulate vascular boundaries and maintain germ cell survival in the ovary...

..See research article http://www.biomedcentral.com/1741-7007/8/113...

..These results indicate that Pin1 regulates the timing of PGC proliferation during mouse embryonic development...

..In this article we focus on signals in the male gonad that first are responsible for the specification of Sertoli cells, and second for the specification and patterning of interstitial cells...

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..Work is underway to identify genes controlling these processes. These genes will then be linked to Sry...

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..Current experiments in the lab address the hypothesis that cord formation and germ cell entry into meiosis are competing pathways in gonad development...

..Using these two Cre lines, we provide the first genetic evidence that Fgfr2 plays distinct roles in proliferation and Sertoli cell differentiation during testis development...

..This work identifies PDGF signaling through the alpha receptor as an important event downstream of Sry in testis organogenesis and Leydig cell differentiation...

..Our results reveal the complex transcription architecture underlying sex determination, and provide a mechanism by which individuals may be sensitized for sex reversal...

..Recently, several of the molecular signals that direct these processes have been identified. In addition, the pathways that suppress features of testis development in the XX gonad are being elucidated...

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..However, recent evidence reveals expression differences between XX and XY brains prior to the time that hormones are circulating, suggesting that some influences on brain development may be autonomous to the cells of the brain...

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..This system would be highly responsive to changes in the upstream primary signal and may provide a basis for the rapid evolution of and transitions between different methods of sex determination...

..Understanding how critical genes in sex determining pathways evolved and how they function in lower vertebrates is expected to improve diagnosis and treatment of human disorders. ..

..In addition, the molecular signals that control or repress the growth of vasculature into a tissue are of critical concern for the design of therapies in the fields of wound healing and tumor biology. ..

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..Moreover, it serves as a general model of how the development of diverse vascular phenotypes is signaled and integrated with organogenesis throughout the embryo. ..

..Although DND1 is specific to germ cells, we anticipate that the regulatory mechanisms involved may be common to many pluripotent stem cell populations. ..