Functional Genomic Identification of Genes Required for Male Gonadal Differentiation in <i>Caenorhabditis elegans</i>

Wnt signaling is tightly regulated during animal development and controls cell proliferation and differentiation. In C. elegans, activation of Wnt signaling alters the activity of the TCF/LEF transcription factor, POP-1, through activation of the Wnt/β-catenin or Wnt/β-catenin asymmetry pathways. In this study, we have identified CACN-1 as a potential regulator of POP-1 in C. elegans larval development. CACN-1/Cactin is a well-conserved protein of unknown molecular function previously implicated in the regulation of several developmental signaling pathways. Here we have used activation of POPTOP, a POP-1-responsive reporter construct, as a proxy for Wnt signaling. POPTOP requires POP-1 and SYS-1/β-catenin for activation in L4 uterine cells. RNAi depletion experiments show that CACN-1 is needed to prevent excessive activation of POPTOP and for proper levels and/or localization of POP-1. Surprisingly, high POPTOP expression correlates with increased levels of POP-1 in uterine nuclei, suggesting POPTOP may not mirror endogenous gene expression in all respects. Genetic interaction studies suggest that CACN-1 may act partially through LIT-1/NLK to alter POP-1 localization and POPTOP activation. Additionally, CACN-1 is required for proper proliferation of larval seam cells. Depletion of CACN-1 results in a loss of POP-1 asymmetry and reduction of terminal seam cell number, suggesting an adoption of the anterior, differentiated fate by the posterior daughter cells. These findings suggest CACN-1/Cactin modulates Wnt signaling during larval development.

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“…Our data are consistent with previous results [41] showing that POPTOP expression is dependent on POP-1 (P<0.0001, n = 16; Fig. 3A).…”

Section: Resultssupporting

confidence: 94%

CACN-1/Cactin Plays a Role in Wnt Signaling in C. elegans

et al. 2014

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“…RSPOs are expressed in vertebrates and invertebrates, such as hemichordates, chordates, and echinoderms, but screening of Drosophila melanogaster and Caenorhabditis elegans failed to identify any RSPO homolog (Yoon & Lee 2012). However, the WNT/b-catenin pathway is required for male cell fate commitment in the gonad of C. elegans (Kalis et al 2010). …”

Section: R105mentioning

confidence: 99%

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

Chassot¹,

Gillot²,

Chaboissier³

2014

Reproduction

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Sex differentiation is a unique developmental process. Starting from a bipotential gonad, it gives rise to the ovary and the testis, two highly specialized organs that differ morphologically and physiologically despite sharing common reproductive and endocrine functions. This highlights the specific plasticity of the gonadal precursors and the existence of complex antagonistic genetic regulation. Mammalian sex determination is controlled by paternal transmission of the Y-linked gene, sex-determining region Y (SRY). Using mouse models, it has been shown that the main role of Sry is to activate the expression of the transcription factor Sox9; either one of these two genes is necessary and sufficient to allow testicular development through Sertoli cell differentiation. Thus, defects in SRY/Sry and/or SOX9/Sox9 expression result in male-to-female sex reversal of XY individuals. Molecular mechanisms governing ovarian differentiation remained unknown for a long time, until the discovery of the roles of R-spondin1 (RSPO1) and WNT4. In XX individuals, activation of the b-catenin signaling pathway by the secreted proteins RSPO1 and WNT4 is required to allow granulosa cell differentiation and, in turn, ovarian differentiation. Thus, mutations in RSPO1 result in female-to-male sex reversal of XX patients, and mouse models have allowed the identification of genetic cascades activated by RSPO1 and WNT4 to regulate ovarian development. In this review, we will discuss the respective roles of RSPO1, WNT4, and the b-catenin signaling pathway during ovarian differentiation in mice.Reproduction (2014) 148 R97-R110

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Section: Sex-biased Expression Of C Elegans X 357 Resultsmentioning

confidence: 99%

“…The XX male strain CB5362 contains tra-2(ar221) that results in male sexual fate and xol-1 (y9) that enhances masculinization (Hodgkin 2002). Because tra-2 is downstream of DCC activation, dosage compensation is still activated in these XX males (Hodgkin 2002;Chandler et al 2009;Kalis et al 2010).To determine expression differences due to sex-specific gene regulation, we compared gene expression between XX hermaphrodites and XX males and between XO hermaphrodites and XO males ( Figure 1B). To determine expression differences due to X chromosome dose, we compared expression between XX and XO hermaphrodites and between XX and XO males.…”

mentioning

confidence: 99%

Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

Kramer¹,

Rao²,

Ercan

2016

Genetics

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Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function.KEYWORDS dosage compensation; C. elegans; RNA-seq; sex; sex-biased gene expression; chromatin; X chromosome; transcription; gene regulation; germline; XO; genetics of sex M ALES and females exhibit many phenotypic differences, termed sexual dimorphisms. With the exception of the gene-poor Y chromosome, the two sexes share identical genomes. Thus, sexual dimorphisms stem from differences in gene expression between sexes. Genes that are expressed differently between sexes include those expressed exclusively (sex specific) or at a higher level in one sex (sex biased). Sexbiased expression allows a gene to be more active in the sex that it benefits without a potential cost to the opposite sex. Sex-biased gene expression is common throughout metazoans. Previous studies indicate up to 60% of all genes show sex-biased expression [in mice (Khil et al. 2004;Yang et al. 2006;Reinius et al. 2012), flies (Parisi et al. 2003;Ranz et al. 2003;Allen et al. 2013;Kaiser and Bachtrog 2014), and nematodes (Reinke et al. 2004;Thomas et al. 2012;Albritton et al. 2014)].Previous genome-wide studies found that compared to autosomes, the X chromosome generally harbors more genes with female-biased expression and fewer genes with malebiased expression [in mice (Khil et al. 2004;Yang et al. 2006;Reinius et al. 2012), flies (Parisi et al. 2003;Ranz et al. 2003), and nematodes (Reinke et al. 2004;Thomas et al. 2012;Albritton et al. 2014)]. However, this observed enrichment of female bias and depletion of male bias from the X is a gene...

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Functional Genomic Identification of Genes Required for Male Gonadal Differentiation in Caenorhabditis elegans

Cited by 27 publications

References 42 publications

CACN-1/Cactin Plays a Role in Wnt Signaling in C. elegans

CACN-1/Cactin Plays a Role in Wnt Signaling in C. elegans

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

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