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Human Molecular Genetics, 2000, Vol. 9, No. 10 1553-1560
© 2000 Oxford University Press

Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development

Sean Grimmond1,+, Nick Van Hateren1, Pam Siggers1, Ruth Arkell1, Rachel Larder1, Marcelo Bento Soares2,3, Maria de Fatima Bonaldo2, Lee Smith1, Zuzanna Tymowska-Lalanne1, Christine Wells1,§ and Andy Greenfield1,¶

1MRC Mammalian Genetics Unit, Harwell, Didcot OX11 0RD, UK, 2Department of Pediatrics and 3Departments of Physiology and Biophysics, The University of Iowa, 451 Eckstein Medical Research Building, Iowa City, IA 52242, USA

The mammalian sex-determining pathway is controlled by the presence or absence of SRY expression in the embryonic gonad. Expression of SRY in males is believed to initiate a pathway of gene expression resulting in testis development. In the absence of SRY, ovary development ensues. Several genes have now been placed in this pathway but our understanding of it is far from complete and several functional classes of protein appear to be absent. Sex-determining genes frequently exhibit sexually dimorphic patterns of expression in the developing gonad both before and after overt differentiation of the testis or ovary. In order to identify additional sex-determining or gonadal differentiation genes we have examined gene expression in the developing gonads of the mouse using cDNA microarrays constructed from a normalized urogenital ridge library. We screened for genes exhibiting sexually dimorphic patterns of expression in the gonad at 12.5 and 13.5 days post-coitum, after overt gonad differentiation, by comparing complex cDNA probes derived from male and female gonadal tissue at these stages on micro­arrays. Using in situ hybridization analysis we show here that two genes identified by this screen, protease nexin-1 (Pn-1) and vanin-1 (Vnn1), exhibit male-specific expression prior to overt gonadal differentiation and are detected in the somatic portion of the developing gonad, suggesting a possible direct link to the testis-determining pathway for both genes.

+ Present address: Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston QLD 4029, Australia

§ Present address: Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane QLD 4072, Australia

To whom correspondence should be addressed. Tel: +44 1235 824 544; Fax +44 1235 834 776; Email: a.greenfield@har.mrc.ac.uk


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