Abstract
In contrast to the developing testis, molecular pathways driving fetal ovarian development have been difficult to characterise. To date no single master regulator of ovarian development has been identified that would be considered the female equivalent of Sry. Using a genomic approach we identified a number of novel protein-coding as well as non-coding genes that were detectable at higher levels in the ovary compared to testis during early mouse gonad development. We were able to cluster these ovarian genes into different temporal expression categories. Of note, Lrrc34 and AK015184 were detected in XX but not XY germ cells before the onset of sex-specific germ cell differentiation marked by entry into meiosis in an ovary and mitotic arrest in a testis. We also defined distinct spatial expression domains of somatic cell genes in the developing ovary. Our data expands the set of markers of early mouse ovary differentiation and identifies a classification of early ovarian genes, thus providing additional avenues with which to dissect this process.
Highlights
Despite the importance of the ovary for reproduction through the production of oocytes and the secretion of female sex hormones, its development during embryogenesis remains poorly understood
In order to identify novel genes that are expressed at higher levels in the ovary compared to testis during mouse gonad development, we interrogated published microarray data from whole gonads at 14.5 days post coitum (NCBI GEO database accession GSE5334 and GSE4818 and GUDMAP database at http://www.gudmap.org) as well as microarray data of isolated supporting cells at 13.5 dpc ([25]; GEO: GSE4928) using B statistics
To validate the dynamics and sex-specificity of expression of these genes, we performed quantitative real-time RT-PCR of mRNA extracted from embryonic gonads from 11.5 to 13.5 dpc using the ovarian gene Foxl2 as an XX control ([31], Figure 1N) and the testicular gene Amh as an XY control ([32], Figure 1O)
Summary
Despite the importance of the ovary for reproduction through the production of oocytes and the secretion of female sex hormones, its development during embryogenesis remains poorly understood. The expression of the male-determining gene Sry (sexdetermining region of chromosome Y) is initiated in the XY gonad, driving the differentiation of the genital ridges into testes [1,2]. Sry expression induces the differentiation of Sertoli cells, which are considered to be the organizers of testis differentiation. They produce key signalling molecules that influence the differentiation of other testicular cell types leading to characteristic testicular histology [3]. If Sry is absent or fails to act in time, the indifferent gonad differentiates into an ovary, which is driven by a different gene expression program
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