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The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.

Publication ,  Journal Article
Moniot, B; Declosmenil, F; Barrionuevo, F; Scherer, G; Aritake, K; Malki, S; Marzi, L; Cohen-Solal, A; Georg, I; Klattig, J; Englert, C ...
Published in: Development
June 2009

Activation by the Y-encoded testis determining factor SRY and maintenance of expression of the Sox9 gene encoding the central transcription factor of Sertoli cell differentiation are key events in the mammalian sexual differentiation program. In the mouse XY gonad, SOX9 upregulates Fgf9, which initiates a Sox9/Fgf9 feedforward loop, and Sox9 expression is stimulated by the prostaglandin D2 (PGD2) producing lipocalin prostaglandin D synthase (L-PGDS, or PTDGS) enzyme, which accelerates commitment to the male pathway. In an attempt to decipher the genetic relationships between Sox9 and the L-Pgds/PGD2 pathway during mouse testicular organogenesis, we found that ablation of Sox9 at the onset or during the time window of expression in embryonic Sertoli cells abolished L-Pgds transcription. By contrast, L-Pgds(-/-) XY embryonic gonads displayed a reduced level of Sox9 transcript and aberrant SOX9 protein subcellular localization. In this study, we demonstrated genetically that the L-Pgds/PGD2 pathway acts as a second amplification loop of Sox9 expression. Moreover, examination of Fgf9(-/-) and L-Pgds(-/-) XY embryonic gonads demonstrated that the two Sox9 gene activity amplifying pathways work independently. These data suggest that, once activated and maintained by SOX9, production of testicular L-PGDS leads to the accumulation of PGD2, which in turn activates Sox9 transcription and nuclear translocation of SOX9. This mechanism participates together with FGF9 as an amplification system of Sox9 gene expression and activity during mammalian testicular organogenesis.

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Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2009

Volume

136

Issue

11

Start / End Page

1813 / 1821

Location

England

Related Subject Headings

  • Testis
  • Sex-Determining Region Y Protein
  • Sex Differentiation
  • Sertoli Cells
  • SOX9 Transcription Factor
  • Prostaglandin D2
  • Mutation
  • Mice
  • Male
  • Lipocalins
 

Citation

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Moniot, B., Declosmenil, F., Barrionuevo, F., Scherer, G., Aritake, K., Malki, S., … Poulat, F. (2009). The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development, 136(11), 1813–1821. https://doi.org/10.1242/dev.032631
Moniot, Brigitte, Faustine Declosmenil, Francisco Barrionuevo, Gerd Scherer, Kosuke Aritake, Safia Malki, Laetitia Marzi, et al. “The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.Development 136, no. 11 (June 2009): 1813–21. https://doi.org/10.1242/dev.032631.
Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, et al. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. 2009 Jun;136(11):1813–21.
Moniot, Brigitte, et al. “The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.Development, vol. 136, no. 11, June 2009, pp. 1813–21. Pubmed, doi:10.1242/dev.032631.
Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. 2009 Jun;136(11):1813–1821.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2009

Volume

136

Issue

11

Start / End Page

1813 / 1821

Location

England

Related Subject Headings

  • Testis
  • Sex-Determining Region Y Protein
  • Sex Differentiation
  • Sertoli Cells
  • SOX9 Transcription Factor
  • Prostaglandin D2
  • Mutation
  • Mice
  • Male
  • Lipocalins