Yet, it is becoming clear that a fine balance of androgen signaling is vital for normal ovary development. determination in reptiles explains expression patterns for orthologs of mammalian sex-determining genes. Many of these genes have evolutionarily conserved expression profiles (i.e., and are expressed at a higher level in developing testes vs. developing ovaries in all species), which ITD-1 suggests functional conservation. However, expression profiling alone does not test gene function and will not identify novel sex-determining genes or gene interactions. For that reason, we provide a prospectus on various techniques that promise to reveal new sex-determining genes and regulatory interactions among these genes. We offer specific examples of novel candidate genes and a new signaling pathway in support of these techniques. while denominator proteins inhibit numerator proteins [Harrison, 2007]. Hence, is usually transcribed and translated in flies with a high X chromosome to autosome ratio (XX:AA individuals become females), but is not expressed in flies with a low X to autosome ratio (XY:AA individuals become males). In contrast to this chromosome-counting mechanism, a single Y-linked gene called sex-determining region of the Y determines sex in mice and most other mammals [Swain and Lovell-Badge, 1999; Wilhelm et al., 2007; Wallis et al., 2008]. This gene acts as a dominant male-determining factor and is not related to any sex-determining genes in flies. Moreover, transcription of is usually regulated by a set of genes (and are also unique: SXL regulates female-specific splicing of transformer mRNA in flies [Lopez, 1998], while SRY induces male-specific transcription of the sex-determining region Y-box 9 gene in mice [Sekido and Lovell-Badge, 2009]. The next gene in the travel pathway, doublesex homolog called doublesex and mab-related transcription factor 1 is usually involved in testis development in mice [Fahrioglu et al., 2006]. However, does not play a pivotal role in sex determination in mice ITD-1 like does in flies. These observations lead to broader questions about sex-determining mechanisms. First, to what extent are sex-determining genes and gene networks evolutionarily conserved or unique? Second, can we reconstruct the specific molecular events responsible for the evolution of different sex-determining mechanisms? Given the extensive divergence between phyla (arthropods vs. chordates), the best way to address these questions is usually to study more closely related organisms that still display diverse modes of sex determination. Reptiles fit these criteria Rabbit Polyclonal to Tubulin beta and represent one of the most interesting groups to study from a phylogenetic perspective [Bull, 1980, 1983; Korpelainen, 1990; Janzen and Paukstis, 1991; Valenzuela, 2004]. At the same time, however, researchers face significant challenges when working with reptiles. In this article, we outline what is known, and what is not known, about sexual differentiation in this group. We focus on the molecular and cellular mechanisms underlying sex determination. Most studies to date have been descriptive in nature and have examined homologs of sex-determining genes first identified in mammals. Such work provides important baseline data on conserved genes and should be encouraged, but it will not identify unique sex-determining genes or novel gene regulatory interactions. Therefore, we also provide a prospectus on alternative approaches that promise to reveal new candidate genes and to elucidate functional interactions among these genes. Sex Determination Although the specific molecular mechanism that determines sex has not been revealed in any reptilian species, general modes of sex determination can be described [Bull, 1980; Janzen and Paukstis, 1991]. An individual’s genotype at one or more loci can control whether it develops testes or ovaries. Species that display this mechanism are said to have genotypic sex determination, or ITD-1 GSD. Species with GSD may or may not have distinct sex chromosomes (ZZ males and ZW females or XY males and XX females). A frequent alternative to GSD is environmentally triggered polyphenism (i.e., a single individual can develop testes or ovaries depending upon environmental conditions). Such species are said to have environmental sex determination, or ESD. Various environmental factors, including photoperiod, social environment, and temperature, influence sex determination across the animal kingdom [Bull, 1983; Korpelainen, 1990]. However, temperature is the only environmental variable that has been conclusively shown to determine sex in reptiles [Bull, 1980; Janzen and Paukstis, 1991; Valenzuela, 2004]. This form of ESD is called temperature-dependent sex determination, or TSD. The overall pattern of evolutionary transitions.?(fig.2B).2B). test gene function and will not identify novel sex-determining genes or gene interactions. For that reason, we provide a prospectus on various techniques that promise to reveal new sex-determining genes and regulatory interactions among these genes. We offer specific examples of novel candidate genes and a new signaling pathway in support of these techniques. while denominator proteins inhibit numerator proteins [Harrison, 2007]. Hence, is transcribed and translated in flies with a high X chromosome to autosome ratio (XX:AA individuals become females), but is not expressed in flies with a low X to autosome ratio (XY:AA individuals become males). In contrast to this chromosome-counting mechanism, a single Y-linked gene called sex-determining region of the Y determines sex in mice and most other mammals [Swain and Lovell-Badge, 1999; Wilhelm et al., 2007; Wallis et al., 2008]. This gene acts as a dominant male-determining factor and is not related to any ITD-1 sex-determining genes in flies. Moreover, transcription of is regulated by a set of genes (and are also unique: SXL regulates female-specific splicing of transformer mRNA in flies [Lopez, 1998], while SRY induces male-specific transcription of the sex-determining region Y-box 9 gene in mice [Sekido and Lovell-Badge, 2009]. The next gene in the fly pathway, doublesex homolog called doublesex and mab-related transcription factor 1 is involved in testis development in mice [Fahrioglu et al., 2006]. However, does not play a pivotal role in sex determination in mice like does in flies. These observations lead to broader questions about sex-determining mechanisms. First, ITD-1 to what extent are sex-determining genes and gene networks evolutionarily conserved or unique? Second, can we reconstruct the specific molecular events responsible for the evolution of different sex-determining mechanisms? Given the extensive divergence between phyla (arthropods vs. chordates), the best way to address these questions is to study more closely related organisms that still display diverse modes of sex determination. Reptiles fit these criteria and represent one of the most interesting groups to study from a phylogenetic perspective [Bull, 1980, 1983; Korpelainen, 1990; Janzen and Paukstis, 1991; Valenzuela, 2004]. At the same time, however, researchers face significant challenges when working with reptiles. In this article, we outline what is known, and what is not known, about sexual differentiation in this group. We focus on the molecular and cellular mechanisms underlying sex determination. Most studies to date have been descriptive in nature and have examined homologs of sex-determining genes first identified in mammals. Such work provides important baseline data on conserved genes and should be encouraged, but it will not identify unique sex-determining genes or novel gene regulatory interactions. Therefore, we also provide a prospectus on alternative approaches that promise to reveal new candidate genes and to elucidate functional interactions among these genes. Sex Determination Although the specific molecular mechanism that determines sex has not been revealed in any reptilian species, general modes of sex determination can be described [Bull, 1980; Janzen and Paukstis, 1991]. An individual’s genotype at one or more loci can control whether it develops testes or ovaries. Species that display this mechanism are said to have genotypic sex determination, or GSD. Species with GSD may or may not have distinct sex chromosomes (ZZ males and ZW females or XY males and XX females). A frequent alternative to GSD is environmentally triggered polyphenism (i.e., a single individual can develop testes or ovaries depending upon environmental conditions). Such species are said to have environmental sex determination, or ESD. Various environmental factors, including photoperiod, social environment, and temperature, influence sex determination across the animal kingdom [Bull, 1983; Korpelainen, 1990]. However, temperature is the only environmental variable that has been conclusively shown to determine sex in reptiles [Bull, 1980; Janzen and Paukstis, 1991; Valenzuela, 2004]. This form of ESD is called temperature-dependent sex determination, or TSD. The overall pattern of evolutionary transitions between GSD and TSD in reptiles is not yet clear, but phylogenetic analyses suggest TSD is an ancestral trait in turtles.