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Submitted on March 16, 2005
Accepted on April 25, 2005
Department of Reproduction and Development, Erasmus MC - University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: m.wijgerde{at}erasmusmc.nl.
Follicle development in the mammalian ovary requires interactions between the oocyte, granulosa cells, and theca cells, co-ordinating 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 (Ihh) and desert hedgehog (Dhh) 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 peri-ovulatory 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, since 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.
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