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1: Hum Mol Genet. 2006 Feb 1;15(3):417-31. Epub 2006 Jan 6.

Expression profiling of purified mouse gonadal somatic cells during the critical 
time window of sex determination reveals novel candidate genes for human sexual
dysgenesis syndromes.

Beverdam A, Koopman P.

Division of Genetics and Developmental Biology, Institute for Molecular
Bioscience, The University of Queensland, Brisbane, Qld 4072, Australia.

Despite the identification of SRY as the testis-determining gene in mammals, the 
genetic interactions controlling the earliest steps of male sex determination
remain poorly understood. In particular, the molecular lesions underlying a high 
proportion of human XY gonadal dysgenesis, XX maleness and XX true
hermaphroditism remain undiscovered. A number of screens have identified
candidate genes whose expression is modulated during testis or ovary
differentiation in mice, but these screens have used whole gonads, consisting of 
multiple cell types, or stages of gonadal development well beyond the time of sex
determination. We describe here a novel reporter mouse line that expresses
enhanced green fluorescent protein under the control of an Sf1 promoter fragment,
marking Sertoli and granulosa cell precursors during the critical period of sex
determination. These cells were purified from gonads of male and female
transgenic embryos at 10.5 dpc (shortly after Sry transcription is activated) and
11.5 dpc (when Sox9 transcription begins), and their transcriptomes analysed
using Affymetrix genome arrays. We identified 266 genes, including Dhh, Fgf9 and 
Ptgds, that were upregulated and 50 genes that were downregulated in 11.5 dpc
male somatic gonad cells only, and 242 genes, including Fst, that were
upregulated in 11.5 dpc female somatic gonad cells only. The majority of these
genes are novel genes that lack identifiable homology, and several human
orthologues were found to map to chromosomal loci implicated in disorders of
sexual development. These genes represent an important resource with which to
piece together the earliest steps of sex determination and gonad development, and
provide new candidates for mutation searching in human sexual dysgenesis
syndromes.

PMID: 16399799 [PubMed - indexed for MEDLINE]

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