File:Mouse gonad sex determination 01.jpg

From Embryology

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Fgf9 is critical to repress Wnt4 and establish the testis pathway during mammalian sex determination

The researchers started by examining Fgf9 expression during normal gonad development in the mouse.

  • E11.5 days - was evenly distributed in the gonads of both sexes
  • E12 days - was found only in XY gonads, and only in Sertoli cells within testis cords and cells near the surface of the gonad.

Every embryonic gonad (at this point, neither ovary nor testis) harbors cells with the potential to choose either fate (male or female). Reflecting this noncommittal approach, both XX and XY gonads initially display similar expression patterns for the sex-determining genes Sox9, Fgf9, and Wnt4. If Sry does not intervene during a critical window in development, the cells will default to the ovarian pathway. Once Sry expression begins, other genes start to choose sides: Sox9 and Fgf9 become active only in male gonads, while Wnt4 becomes active only in female gonads. Loss of Fgf9 in XY mice leads to sex reversal; in XX mice, loss of Wnt4 leads to partial testis development. Only when the protein products of Sry, Sox9, and Fgf9 are all expressed together do male-specific Sertoli cells develop—and prod the developing gonad toward full male differentiation.

See related article:Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R & Capel B. (2006). Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. , 4, e187. PMID: 16700629 DOI.

"The genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9) and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch— Sry in the case of mammals—is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways."

(Above text modified from original PLoS Biol. articles)


Gross L. (2006). Male or female? It depends on the dose. PLoS Biol. , 4, e211. PMID: 20076594 DOI.


© 2006 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation: Gross L (2006) Male or Female? It Depends on the Dose. PLoS Biol 4(6): e211. doi:10.1371/journal.pbio.0040211

Original file name: Journal.pbio.0040211.g001.jpg

Cite this page: Hill, M.A. (2024, May 30) Embryology Mouse gonad sex determination 01.jpg. Retrieved from

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G

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current10:48, 29 May 2011Thumbnail for version as of 10:48, 29 May 2011600 × 600 (81 KB)S8600021 (talk | contribs)==Fgf9 is critical to repress Wnt4 and establish the testis pathway during mammalian sex determination== * red - Sertoli cells. * green - germ cells and endothelial cells. Every embryonic gonad (at this point, neither ovary nor testis) harbors cells wi