
In mammals, the primary step in male sex determination is the initiation of testis development in the bipotential gonad primordium. This step depends on the Y-linked male sex-determining gene, Sry. Expression of Sry in the XY gonad, or as a transgene in an XX gonad, leads to the differentiation of Sertoli cells. Failures in Sertoli cell differentiation in the XY gonad result in sex reversal and ovary formation. In addition to Sertoli cell differentiation, we are studying the signaling pathways between Sry expression and early steps in testis organogenesis using mouse as a model system. Using genetic and cell biology approaches, we determined the origin of several key cell types of the testis. We also identified two pathways, proliferation and cell migration, that are controlled by Sry and lead to the architectural patterning of the testis. Currently we are investigating the novel hypothesis that reciprocal signals between the vasculature and Sertoli cells are involved in patterning testis cords. Testis organogenesis is an ideal model system to study the integration of vasculature during development of organ structure. In addition, we are investigating critical signals between Sertoli cells and germ cells during testis cord formation. Defects in these signals result in teratomas and gonadal blastomas, common neoplasias in young boys. Experimental approaches include the use of molecular and biochemical techniques, mutant mice, transgenics, organ culture assays, differential screens, immunocytochemistry imaging techniques, and classic mouse genetics.
Education and Training
- University of Pennsylvania, Ph.D. 1989
Selected Grants and Awards
- Duke Women's Reproductive Health Research Scholars
- Genetic and Genomics Training Grant
- Identification of a Genetic Pathway Linking Temperature with Epigenetic Control of Gonad Determination in T. scripta
- Building Interdisciplinary Research Careers in Women's Health
- IRES Track 1 IRTG Engaged in Dissecting and Reengineering the Regulatory Genome
- Defining Mechanisms of Ovarian Rescue
- Training Program in Developmental and Stem Cell Biology
- Super-resolution Imaging via Multiple Modalities with the Zeiss Elyra 7
- Bioinformatics and Computational Biology Training Program
- Opposing Pathways in Mammalian Sex Determination
- DND1 Mediated Posttranscriptional Regulation in Murine Prospermatogonia During G1/G0 Arrest
- Genetics Training Grant
- Organization and Function of Cellular Structure
- Mechanisms of ovarian rescue in chemotherapy-treated female mice
- Center for Molecular & Cellular Studies of Ped Disease
- Temporal profiling and functional analysis of temperature-dependent sex determination
- Role of Lamin B Receptor in Male Germ Cell Differentiation and Epigenetic Regulation
- The Seventh International Symposium on the Biology of Vertebrate Sex Determination
- Multidisciplinary Neonatal Training Grant
- Regulation of Germ Cell Pluripotency Through The RNA-Binding Protein, DND1
- A new cell population regulating cell fate and morphogenesis in the mouse testis
- A Functional Assay to Test Conserved Mechanisms of Sex Determination in the Turtle, T. scripta
- WNT4- Mediated Signaling During Mammalian Sex Determination
- Organ Specific Mechanisms of Vascular Development
- Mechanisms of Gonad Organogenesis in the red-eared slider tutle (Trachemys scripta)
- Fourth Annual Symposium on the Biology of Vertebrate Sex Determination
- Zeiss LSM510 META confocal-fluorescence spectroscopy
- Analysis of Sonic Hedgehog Function During Gonadogenesis
- Same