This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wijgerde, M. Articles by Grootegoed, J. A. Search for Related Content PubMed PubMed Citation Articles by Wijgerde, M. Articles by Grootegoed, J. A.

Hedgehog Signaling in Mouse Ovary: Indian Hedgehog and Desert Hedgehog from Granulosa Cells Induce Target Gene Expression in Developing Theca Cells

Department of Reproduction and Development, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Mark Wijgerde, Department of Reproduction and Development, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: m.wijgerde{at}erasmusmc.nl.

Follicle development in the mammalian ovary requires interactions among the oocyte, granulosa cells, and theca cells, coordinating gametogenesis and steroidogenesis. Here we show that granulosa cells of growing follicles in mouse ovary act as a source of hedgehog signaling. Expression of Indian hedgehog and desert hedgehog mRNAs initiates in granulosa cells at the primary follicle stage, and we find induced expression of the hedgehog target genes Ptch1 and Gli1, in the surrounding pre-theca cell compartment. Cyclopamine, a highly specific hedgehog signaling antagonist, inhibits this induced expression of target genes in cultured neonatal mouse ovaries. The theca cell compartment remains a target of hedgehog signaling throughout follicle development, showing induced expression of the hedgehog target genes Ptch1, Ptch2, Hip1, and Gli1. In periovulatory follicles, a dynamic synchrony between loss of hedgehog expression and loss of induced target gene expression is observed. Oocytes are unable to respond to hedgehog because they lack expression of the essential signal transducer Smo (smoothened). The present results point to a prominent role of hedgehog signaling in the communication between granulosa cells and developing theca cells.

This article has been cited by other articles:

				A. Zibat, A. Uhmann, F. Nitzki, M. Wijgerde, A. Frommhold, T. Heller, V. Armstrong, L. Wojnowski, L. Quintanilla-Martinez, J. Reifenberger, et al. Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts Carcinogenesis, June 1, 2009; 30(6): 918 - 926. [Abstract] [Full Text] [PDF]

				Y. Ren, R. G. Cowan, R. M. Harman, and S. M. Quirk Dominant Activation of the Hedgehog Signaling Pathway in the Ovary Alters Theca Development and Prevents Ovulation Mol. Endocrinol., May 1, 2009; 23(5): 711 - 723. [Abstract] [Full Text] [PDF]

				A. C. Kim, F. M. Barlaskar, J. H. Heaton, T. Else, V. R. Kelly, K. T. Krill, J. O. Scheys, D. P. Simon, A. Trovato, W.-H. Yang, et al. In Search of Adrenocortical Stem and Progenitor Cells Endocr. Rev., May 1, 2009; 30(3): 241 - 263. [Abstract] [Full Text] [PDF]

				D. J. Trombly, T. K. Woodruff, and K. E. Mayo Suppression of Notch Signaling in the Neonatal Mouse Ovary Decreases Primordial Follicle Formation Endocrinology, February 1, 2009; 150(2): 1014 - 1024. [Abstract] [Full Text] [PDF]

				Q. Li, F. Jimenez-Krassel, J. J Ireland, and G. W Smith Gene expression profiling of bovine preovulatory follicles: gonadotropin surge and prostanoid-dependent up-regulation of genes potentially linked to the ovulatory process Reproduction, February 1, 2009; 137(2): 297 - 307. [Abstract] [Full Text] [PDF]

				M. C. Russell, R. G. Cowan, R. M. Harman, A. L. Walker, and S. M. Quirk The Hedgehog Signaling Pathway in the Mouse Ovary Biol Reprod, August 1, 2007; 77(2): 226 - 236. [Abstract] [Full Text] [PDF]

				A. Honda, M. Hirose, K. Hara, S. Matoba, K. Inoue, H. Miki, H. Hiura, M. Kanatsu-Shinohara, Y. Kanai, T. Kono, et al. Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells PNAS, July 24, 2007; 104(30): 12389 - 12394. [Abstract] [Full Text] [PDF]

				M A Sarraj, P J McClive, A Szczepny, H Daggag, K L Loveland, and A H Sinclair Expression of Wsb2 in the developing and adult mouse testis Reproduction, April 1, 2007; 133(4): 753 - 761. [Abstract] [Full Text] [PDF]