Global Survey of Protein Expression during Gonadal Sex Determination in Mice

Ewen, Katherine A.; Baker, Mark A.; Wilhelm, Dagmar; Aitken, R. John; Koopman, Peter

doi:10.1074/mcp.m900108-mcp200

Cited by 19 publications

(14 citation statements)

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“…In this case, an mRNA binding protein (LH receptor mRNA-binding protein, LRBP) also participates, which binds the coding region of mRNA of the LH receptor inducing its degradation (Menon et al 2007;Nair et al 2002). Recently a global analysis of the proteome of mouse gonads during the period of sex determination was presented (11.5 and 12.0 dpc), where proteins were identified whose main functions are (1) modification and transport of post-transcriptional RNA, (2) the folding and synthesis of proteins and (3) post-translational modification (Ewen et al 2009). The group of proteins whose function is post-transcriptional modification of RNA includes 31 genes which may be of great interest for the regulation of genes such as 3b-Hsd, which in this study has been shown to be regulated in a post-transcriptional way.…”

Section: Discussionmentioning

confidence: 99%

Expression of 3β-HSD1 and P450 Aromatase enzymes during mouse gonad differentiation

et al. 2011

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In sheep embryos, steroidogenic activity has been reported as taking place during the period of sexual differentiation. In the case of mouse embryos, the sporadic detection or absence of steroidogenic enzymes suggests that the ovary is inactive. The purpose of this work was to establish if mouse undifferentiated gonads express steroidogenic enzymes in a similar way as in sheep embryos. To know this, we analyzed the mRNA expression pattern of 3β-Hsd1 and P450arom as well as protein expression pattern of 3β-HSD1 and Testosterone in normal undifferentiated and differentiated gonads from both male and female mice embryo. Our data indicate that there is expression of 3β-Hsd1 in XX gonads during gonad differentiation period. Nevertheless the Testosterone which would indicate steroidogenic activity is not produced. Besides, the absence of P450arom indicates that the production of Estradiol as observed in the ovaries of sheep does not occur. The detection of 3β-Hsd1 in the early stages of ovarian development, as well as the absence of Testosterone suggests that XX gonads are not steroidogenic and that 3β-Hsd1 enzyme may play a different role than in the steroidogenesis process.

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Section: Discussionmentioning

confidence: 99%

Expression of 3β-HSD1 and P450 Aromatase enzymes during mouse gonad differentiation

et al. 2011

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“…However, similar proteomic studies of internal cell populations have been more difficult and are usually only partially represented in proteomes of whole organs owing to signal dilution (e.g., refs. [11][12][13][14][15][16].…”

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confidence: 99%

The protein expression landscape of the Arabidopsis root

Petricka

Schauer

Megraw

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

157

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Because proteins are the major functional components of cells, knowledge of their cellular localization is crucial to gaining an understanding of the biology of multicellular organisms. We have generated a protein expression map of the Arabidopsis root providing the identity and cell type-specific localization of nearly 2,000 proteins. Grouping proteins into functional categories revealed unique cellular functions and identified cell type-specific biomarkers. Cellular colocalization provided support for numerous protein-protein interactions. With a binary comparison, we found that RNA and protein expression profiles are weakly correlated. We then performed peak integration at cell type-specific resolution and found an improved correlation with transcriptome data using continuous values. We performed GeLC-MS/MS (in-gel tryptic digestion followed by liquid chromatography-tandem mass spectrometry) proteomic experiments on mutants with ectopic and no root hairs, providing complementary proteomic data. Finally, among our root hair-specific proteins we identified two unique regulators of root hair development.plant proteome | cell-type expression | FACS | RNA-protein correlation | root hair mutant M ulticellular organisms use specialized cell types to perform activities that are integral to their function. Cellular tasks are usually achieved by proteins, which act in signaling cascades, provide structural support, and catalyze enzymatic reactions vital to growth and metabolism. Knowledge of protein cellular localization and abundance using proteomic approaches is thus crucial to our understanding of biological systems (1, 2). Proteome data can be visually represented in a map, which highlights the spatial relationships of proteins at the level of cell type, tissue, or organ. Proteome maps are useful representations of the complex "building plan" of a biological system and also serve as valuable tools for the discovery of new cellular functions (2, 3). Proteomic studies of single cell populations isolated from a variety of multicellular organisms have recently been achieved, including the oocytes of worms and mice (4-6); pollen grains (consisting of two sperm and one vegetative cell) and stomatal guard cells of plants (7,8); and sperm cells of mice and flies (9, 10). These cell types were relatively accessible because they either reside on the surface and can be purified in large quantities using biochemical fractionation (e.g., guard cells) or are large and can easily be collected (e.g., Caenorhabditis elegans oocytes). However, similar proteomic studies of internal cell populations have been more difficult and are usually only partially represented in proteomes of whole organs owing to signal dilution (e.g., refs. 11-16).The Arabidopsis thaliana root is an excellent model for investigating cellular functions internal to an organ because it is transparent, radially symmetric, and cell types can be isolated by FACS to allow molecular profiling (17). The goal of this study was to investigate cell-type function by genera...

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“…Similarly, mapping studies in other mouse strains are being aided by the recently completed full sequences for 17 common inbred strains60 and accurate imputed full sequences (from high density genotype datasets) for over 100 additional strains 61,62. As genome‐wide analysis platforms continue to improve and lower in cost, it is feasible for a single investigator to quantify genetic variation (including alternative splicing and copy number variants63–65) and molecular phenotypes (e.g., mRNA4,5,66/protein67 abundance) across the genome at single nucleotide resolution. These systems‐level analyses are becoming increasingly common in the field of sex determination.…”

Section: Resultsmentioning

confidence: 99%

Sex and the circuitry: progress toward a systems‐level understanding of vertebrate sex determination

Munger

Capel

2012

WIREs Mechanisms of Disease

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In vertebrates, the gonad arises as a bipotential primordium that can differentiate as a testis or ovary. Cells are initially primed to adopt either fate by balanced antagonistic signaling pathways and transcription networks. Sexual fate is determined by activating the testis or ovarian pathway and repressing the alternative pathway. A complex, dynamic transcription network underlies this process, as approximately half the genome is being transcribed during this period, and many genes are expressed in a sexually dimorphic manner. This network is highly plastic, however multiple lines of evidence suggest that many elements of the pathway converge on the stabilization or disruption of Sox9 expression. The single gene mutational approach has led to the identification of ~30 additional genes involved in vertebrate sex determination. However,>50% of human disorders of sexual development (DSDs) are not explained by any of these genes, suggesting many critical elements of the system await discovery. Emerging technologies and genetic resources enable the investigation of the sex determination network on a global scale in the context of a variable genetic background or environmental influences. Using these new tools we can investigate how cells establish a bipotential state that is poised to adopt either sexual fate, and how they integrate multiple signaling and transcriptional inputs to drive a cell fate decision. Elucidating the genetic architecture underlying sex determination in model systems can lead to the identification of conserved modules correlated with phenotypic outcomes, and critical pressure points in the network that predict genes involved in DSDs in humans.

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Global Survey of Protein Expression during Gonadal Sex Determination in Mice

Cited by 19 publications

References 135 publications

Expression of 3β-HSD1 and P450 Aromatase enzymes during mouse gonad differentiation

Expression of 3β-HSD1 and P450 Aromatase enzymes during mouse gonad differentiation

The protein expression landscape of the Arabidopsis root

Sex and the circuitry: progress toward a systems‐level understanding of vertebrate sex determination

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