General introduction to our research back forward
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THE QUESTION of how genes orchestrate the complex development of the embryo is a major focus of modern biology. During development, cells must differentiate to acquire specialized functions, move to their appropriate position in the embryo and establish communication with their neighbours in order to act coordinately in functional tissues. Our work is aimed at isolating genes involved in organ formation, and studying their expression, regulation, function and interaction in the developing embryo.

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A major area of interest is the genetic control of mammalian sex determination - how we develop as males or females. This boils down to a study of how testes or ovaries develop in the embryo. In many ways this is a unique system to study, since the primitive gonad tissue is the only tissue in the embryo that can adopt either of two possible fates (testis or ovary), depending on the genetic signals received. In many other ways, testis and ovary development are typical in that they use similar genetic networks to those that regulate the development of any other organ, and so our studies can inform, and be informed by, many other aspects of developmental biology.

Whichever way you look at it, the allocation of male or female sex in the embryo is a critical fork in the road, that profoundly influences who we are and how we live. Equally importantly, defects in sexual development are among the most common forms of inherited disorders, and the repercussions – including functional, psychological and social consequences of ambiguous sexual identity - often present a major crisis for those directly affected and for their families. Our research not only probes the fundamental differences between male and female, which continue to intrigue people of all ages, but also provides a basis for diagnosis, counselling and management of intersex disorders.

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Through our interest in gonadal development, we have begun to examine the development of germ cells that ultimately generate the sperm or egg cells. These cells are uniquely important in that they carry our genes from generation to generation. We are examining how germ cell specification and differentiation is regulated, with the aims of identifying genes involved in testicular and childhood cancers, uncovering mechanisms underlying male infertility, developing new approaches to transgenic animal production, identification new targets for pest control, reprogramming germ cells for applications in biotechnology, and formulating innovative strategies for enhancing or suppressing fertility.

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One group of genes has been found to play a particularly important role in sex determination. These genes, called Sox genes (Sry-type HMG-box genes) encode transcription factors with diverse roles in cell differentiation and embryo development. The Sox gene family comprises 20 genes in humans and mice, and is found in a wide diversity of organisms. We have identified several members of this gene family and are examining their roles in the mouse embryo, using a range of techniques such as in situ hybridization, transgenic mouse production and gene targeting in embryonic stem cells. Studying the biochemical functions of the SOX transcription factors is important for understanding how different types of cells arise in a large number of organ systems. Sox genes identified in our laboratory are important for proper development of blood vessels, the skeleton, kidneys, brain and many other tissues.