Hedgehog signaling in mouse ovary: Indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells.
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.
Wijgerde
Mark
M
Department of Reproduction and Development, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. m.wijgerde@erasmusmc.nl
Ooms
Marja
M
Hoogerbrugge
Jos W
JW
Grootegoed
J Anton
JA
D000818:Animals; D000831:Animals, Newborn; D004627:Embryonic Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D010053:Ovary / Q000254:growth & development / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013480:Superovulation; D013799:Theca Cells / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; C000606240:Ptch1 protein, mouse; C000606241:Ptch2 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015534:Trans-Activators