Mammalian sex determination: a molecular drama

  1. Amanda Swain and
  2. Robin Lovell-Badge
  1. Division of Developmental Genetics, Medical Research Council (MRC), National Institute for Medical Research, London NW7 1AA, UK; Section of Gene Function and Regulation, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, UK

This extract was created in the absence of an abstract.

Our knowledge of mammalian sex determination is based on two main areas of study. First, the characterization of the biological events that determine the sexual development of the individual, including patterns of gene expression, and second, the study of genetic mutations in humans and mice that lead to abnormal sexual phenotypes. In the search for molecular components of this process, the identification of genes in loci involved in human disease has been especially fruitful. Serendipity has also played a hand, where in several cases targeted mutations in mouse genes, being studied for other reasons, have led to unexpected sex reversal phenotypes. The collection of molecular candidates implicated in sex determination is now quite extensive. We are not able to fit all of these into simple pathways, where one gene acts on the next and so on in a linear fashion, as seems possible in the invertebrate model organisms,Caenorhabditis elegans and Drosophila. In part this is due to gaps in our knowledge, as we are clearly missing several key components, but it is looking increasingly likely that the system is much better described as a network of factors. In fact, the story so far is like some partly recovered script for a play. Thus some gene products are main characters with roles at several different stages, some act as a chorus, in a combinatorial fashion with others, whereas a few play a critical role in one scene and then disappear. The mechanism presumably evolved to be delicately poised to respond to the initial trigger to be male or female and then to amplify this decision while avoiding development of intersex phenotypes. It is therefore likely to be a system full of back-ups and functional redundancy. The complexity may also follow from the relatively late embryonic stage at which the …

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