Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells.
Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determination of ovarian surface epithelium, granulosa cells and theca cells. Although the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1(+) cells indigenous to the ovary and Gli1(+) mesenchymal cells that migrate from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca.
1] Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana Illinois, USA [2] Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, USA.
Chang
C
Liu
1] Departments of Pathology &Immunology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [2] Centers for Drug Discovery and Reproductive Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Jia
J
Peng
1] Departments of Pathology &Immunology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [2] Centers for Drug Discovery and Reproductive Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [3] Departments of Molecular &Cellular Biology and Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA.
Martin M
MM
Matzuk
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, USA.
Humphrey H-C
HH
Yao
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D055429:Growth Differentiation Factor 9 / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008650:Mesonephros / Q000166:cytology; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D009924:Organ Culture Techniques; D010053:Ovary / Q000196:embryology*; D012097:Repressor Proteins / Q000378:metabolism; D013799:Theca Cells; D059467:Transcriptome; D025721:WT1 Proteins; D000071676:Zinc Finger Protein GLI1
C525898:Gdf9 protein, mouse; C498520:Gli1 protein, mouse; D055429:Growth Differentiation Factor 9; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D025721:WT1 Proteins; C000602896:WT1 protein, mouse; D000071676:Zinc Finger Protein GLI1