Abstract
The development of an embryo as male or female depends on differentiation of the gonads as either testes or ovaries. A number of genes are known to be important for gonadal differentiation, but our understanding of the regulatory networks underpinning sex determination remains fragmentary. To advance our understanding of sexual development beyond the transcriptome level, we performed the first global survey of the mouse gonad proteome at the time of sex determination by using two-dimensional nanoflow LC-MS/MS. The resulting data set contains a total of 1037 gene products (154 non-redundant and 883 redundant proteins) identified from 620 peptides. Functional classification and biological network construction suggested that the identified proteins primarily serve in RNA post-transcriptional modification and trafficking, protein synthesis and folding, and post-translational modification. The data set contains potential novel regulators of gonad development and sex determination not revealed previously by transcriptomics and proteomics studies and more than 60 proteins with potential links to human disorders of sexual development.
Highlights
The development of an embryo as male or female depends on differentiation of the gonads as either testes or ovaries
Expression of SRY up-regulates SRY box containing gene 9 (Sox9) expression beginning around 11.5 dpc; Sex determining region of Chr1 Y (Sry) and Sox9 are both necessary and sufficient for testis determination (6 –11), implying that one or both genes activates a suite of targets in the testis-determining pathway
We identified a total of 620 peptides from the combined lists for the male and female embryonic gonads: 296 (48%) were common to both sexes, 324 (52%) were unique to males, and none were unique to females
Summary
The development of an embryo as male or female depends on differentiation of the gonads as either testes or ovaries. A number of genes are known to be important for gonadal differentiation, but our understanding of the regulatory networks underpinning sex determination remains fragmentary. The data set contains potential novel regulators of gonad development and sex determination not revealed previously by transcriptomics and proteomics studies and more than 60 proteins with potential links to human disorders of sexual development. By 12.5 dpc the testis is organized into cords and interstitial compartments, whereas the ovary has no definable structure at this stage. The timing of these events in testis differentiation correlates with the activity of Sry and its target gene, SRY box containing gene 9 (Sox). Our understanding of the control of ovary differentiation remains limited
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