Gonadal defects in Cited2 -mutant mice indicate a role for SF1 in both testis and ovary differentiation

Combes, Alexander N., Spiller, Cassy M., Harley, Vincent R., Sinclair, Andrew H., Dunwoodie, Sally L., Wilhelm, Dagmar and Koopman, Peter (2010) Gonadal defects in Cited2 -mutant mice indicate a role for SF1 in both testis and ovary differentiation. International Journal of Developmental Biology, 54 4: 683-689. doi:10.1387/ijdb.092920ac

Author Combes, Alexander N.
Spiller, Cassy M.
Harley, Vincent R.
Sinclair, Andrew H.
Dunwoodie, Sally L.
Wilhelm, Dagmar
Koopman, Peter
Title Gonadal defects in Cited2 -mutant mice indicate a role for SF1 in both testis and ovary differentiation
Journal name International Journal of Developmental Biology   Check publisher's open access policy
ISSN 0214-6282
Publication date 2010-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1387/ijdb.092920ac
Open Access Status Not yet assessed
Volume 54
Issue 4
Start page 683
End page 689
Total pages 7
Place of publication Bilbao, Spain
Publisher Universidad del Pais Vasco, Servicio Editorial
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract Sex determination is regulated by a molecular antagonism between testis- and ovary-determining pathways in the supporting cell lineage of the gonadal primordia. Genes important for maintaining this lineage play critical roles in early gonadal development, but their influence on testis and ovary differentiation is unclear due to the severity of loss-of-function phenotypes. The transcription factor SF1 (Nr5a1/Ad4BP) is one such factor, required for establishing the supporting cell lineage, and for propagating the male pathway. In the gonad, Sf1 expression is enhanced by the transcriptional co-factor Cited2. We have used the reduced levels of Sf1 expression in Cited2 -/- mice as a hypomorphic model to gain insight into the sex-specific roles of SF1 function in gonadal development. In XY mutant mice, we found that testis development was delayed in Cited2 -/- gonads, and that testis structure was permanently disrupted. In XX Cited2 -/- gonads, ectopic cell migration was observed which correlated with a transient upregulation of Fgf9, and a delay in Wnt4 then Foxl2 expression. These data suggest a novel role for SF1 in promoting ovarian development in addition to its roles in testis differentiation.
Keyword Cited2
Testis Development
Ovary development
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published Online 24 July 2009

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Created: Thu, 25 Feb 2010, 21:39:04 EST by Susan Allen on behalf of Institute for Molecular Bioscience