Double nexus--Doublesex is the connecting element in sex determination

Verhulst, Eveline C.; Zande, Louis van de

doi:10.1093/bfgp/elv005

Cited by 90 publications

(96 citation statements)

References 107 publications

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“…These two transcription factor proteins have a common DNA binding domain, but different C-terminal domains. In males, Dsx M activates the expression of male differentiation genes and represses female differentiation genes, whereas, in females, Dsx F activates female differentiation genes and represses male differentiation genes (Verhulst and van de Zande, 2015). Thus, Dsx is the downstream effector of the sex determination cascade in Drosophila , regulating the differentiation of sex-specific cell types.…”

Section: Introductionmentioning

confidence: 99%

Dmrt1 is necessary for male sexual development in zebrafish

Webster

Schach

Ordaz

et al. 2017

Developmental Biology

238

178

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The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosomes may evolve.

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Section: Introductionmentioning

confidence: 99%

Dmrt1 is necessary for male sexual development in zebrafish

Webster

Schach

Ordaz

et al. 2017

Developmental Biology

238

178

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“…The genes at the level of the bottom switch appear more conserved than the upstream signals, in line with Wilkins' hypothesis that the cascade evolves from the bottom up (Wilkins, ). In insects, doublesex ( dsx ) has been identified in a range of insect species at the bottom of the sex determination cascade (Shukla & Nagaraju, ; Verhulst & van de Zande, ). It belongs to a group of DNA‐binding motif (DM) encoding genes that are present amongst Metazoa and appear to play a role in sex determination of both invertebrates and vertebrates (Matson & Zarkower, ).…”

Section: Introductionmentioning

confidence: 99%

Maternal provision of non‐sex‐specific transformer messenger RNA in sex determination of the wasp Asobara tabida

Geuverink

Verhulst

Leussen

et al. 2017

Insect Molecular Biology

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In many insect species maternal provision of sex-specifically spliced messenger RNA (mRNA) of sex determination genes is an essential component of the sex determination mechanism. In haplodiploid Hymenoptera, maternal provision in combination with genomic imprinting has been shown for the parasitoid Nasonia vitripennis, known as maternal effect genomic imprinting sex determination (MEGISD). Here, we characterize the sex determination cascade of Asobara tabida, another hymenopteran parasitoid. We show the presence of the conserved sex determination genes doublesex (dsx), transformer (tra) and transformer-2 (tra2) orthologues in As. tabida. Of these, At-dsx and At-tra are sex-specifically spliced, indicating a conserved function in sex determination. At-tra and At-tra2 mRNA is maternally provided to embryos but, in contrast to most studied insects, As. tabida females transmit a non-sex-specific splice form of At-tra mRNA to the eggs. In this respect, As. tabida sex determination differs from the MEGISD mechanism. How the paternal genome can induce female development in the absence of maternal provision of sex-specifically spliced mRNA remains an open question. Our study reports a hitherto unknown variant of maternal effect sex determination and accentuates the diversity of insect sex determination mechanisms.

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“…The interested reader is addressed to the comprehensive overview of Verhulst and Van De Zande (2015) for a discussion on the evolutionary relationship between gene dsx and its many target genes.…”

Section: Comparison Of the Dsx Proteins Of Sciara With Those Of Othermentioning

confidence: 99%

An Unusual Role fordoublesexin Sex Determination in the DipteranSciara

et al. 2015

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The gene doublesex, which is placed at the bottom of the sex-determination gene cascade, plays the ultimate discriminatory role for sex determination in insects. In all insects where this gene has been characterized, the dsx premessenger RNA (premRNA) follows a sex-specific splicing pattern, producing male-and female-specific mRNAs encoding the male-DSXM and female-DSXF proteins, which determine male and female development, respectively. This article reports the isolation and characterization of the gene doublesex of dipteran Sciara insects. The Sciara doublesex gene is constitutively transcribed during development and adult life of males and females. Sciara had no sex-specific doublesex mRNAs but the same transcripts, produced by alternative splicing of its primary transcript, were present in both sexes, although their relative abundance is sex specific. However, only the female DSXF protein, but not the male DSXM protein, was produced at similar amounts in both sexes. An analysis of the expression of female and male Sciara DSX proteins in Drosophila showed that these proteins conserved female and male function, respectively, on the control of Drosophila yolk-protein genes. The molecular evolution of gene doublesex of all insects where this gene has been characterized revealed that Sciara doublesex displays a considerable degree of divergence in its molecular organization and its splicing pattern with respect to the rest of dipterans as suggested by its basal position within the doublesex phylogeny. It is suggested that the doublesex gene is involved in Sciara sex determination although it appears not to play the discriminatory role performed in other insects.KEYWORDS sex determination; molecular evolution; Sciara; gene doublesex; genetics of sex M ALES and females are different at the morphological, physiological, and behavioral levels. This sexual dimorphism results from the integration of two processes: sex determination and sexual differentiation. Sex determination refers to the developmental program that commits the embryo to either the male or the female pathway. The genes underlying this phenomenon are the sex-determination genes. Sexual differentiation refers to the expression of the sex cytodifferentiation genes (which are controlled by the sex-determination genes), the expression of which gives rise to the formation of the sexually dimorphic structures that characterize the male and female adults.The animal kingdom possesses a wealth of mechanisms by which sex is decided (Bull 1983;Beukeboom and Perrin 2014). These mechanisms can be classified into three main categories, depending on the origin of the primary sexdetermination signal, which can be zygotic, maternal, or environmental. These three primary signals occur and are concatenated in the dipteran Sciara (for details see Sánchez 2010). Briefly, in Sciara, sex determination follows the XX/X0 mechanism: XX zygotes will develop as females and X0 zygotes will develop as males. Yet, the final chromosome constitution of the zygote, which start...

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Double nexus--Doublesex is the connecting element in sex determination

Cited by 90 publications

References 107 publications

Dmrt1 is necessary for male sexual development in zebrafish

Dmrt1 is necessary for male sexual development in zebrafish

Maternal provision of non‐sex‐specific transformer messenger RNA in sex determination of the wasp Asobara tabida

An Unusual Role fordoublesexin Sex Determination in the DipteranSciara

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