QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online May 8, 2009
doi: 10.1242/10.1242/dev.032631

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Moniot, B. Articles by Poulat, F. PubMed Articles by Moniot, B. Articles by Poulat, F. Social Bookmarking                         What's this?

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

Brigitte Moniot^1,*, Faustine Declosmenil^1,*, Francisco Barrionuevo², Gerd Scherer², Kosuke Aritake³, Safia Malki^1,, Laetitia Marzi¹, Anne Cohen-Solal⁴, Ina Georg², Jürgen Klattig⁵, Christoph Englert⁵, Yuna Kim⁶, Blanche Capel⁶, Naomi Eguchi³, Yoshihiro Urade³, Brigitte Boizet-Bonhoure^1,, and Francis Poulat^1,,

¹ Department of Genetics and Development, Institut de Génétique Humaine CNRS UPR1142, 34396 Montpellier, Cedex5, France.
² Institute of Human Genetics and Anthropology, University of Freiburg, Germany.
³ Osaka Bioscience Institute, 565-0874 Osaka, Japan.
⁴ Institut de Génomique Fonctionnelle CNRS UMR5203, Montpellier, France.
⁵ Leibniz Institute for Age Research, Fritz Lipmann Institute, 07745 Jena, Germany.
⁶ Duke University Medical Center, Durham, NC 27710, USA.

Authors for correspondence (e-mails: boizet{at}igh.cnrs.fr; francis{at}igh.cnrs.fr)

Accepted 24 March 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.

Key words: SOX9, PGD2, FGF9, Sertoli cell, Testis organogenesis, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				T. Kumasaka, K. Aritake, H. Ago, D. Irikura, T. Tsurumura, M. Yamamoto, M. Miyano, Y. Urade, and O. Hayaishi Structural Basis of the Catalytic Mechanism Operating in Open-Closed Conformers of Lipocalin Type Prostaglandin D Synthase J. Biol. Chem., August 14, 2009; 284(33): 22344 - 22352. [Abstract] [Full Text] [PDF]