Lineage specification of ovarian theca cells requires multi-cellular interactions via oocyte and granulosa cells

Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determinations of ovarian surface epithelium, granulosa cells, and theca cells. While the sources of ovarian surface epithelium and granulosa cells are known, the embryonic origin(s) of theca stem/progenitor cells have not been definitively identified. Here I show that theca cells derive from two sources: Wt1-positive cells indigenous to the ovary and Gli1-positive mesenchymal cells that migrate from the mesonephros. These two theca progenitor populations are distinct in their cell lineage contributions, relative proximity to granulosa cells, and their gene expression profiles. The two sources of theca progenitors acquire theca lineage marker Gli1 in the ovary soon after birth, in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibited a loss of theca layer, 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. Gdf9 ablation resulted in diminished expression of Dhh, Ihh, and theca cell-specific Gli1. Conversely, supplementation of GDF9 to oocyte-depleted ovaries reactivated Dhh/Ihh production and subsequent expression of Gli1. My studies provide the first genetic evidence for the origins of theca cells and reveal a novel multicellular interaction via GDF9 and Hedgehog signaling critical for ovarian folliculogenesis and formation of a functional theca.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Liu, Chang

Contributors dc:contributor

• Yao, Humphrey H-C.
• Bahr, Janice M.
• Miller, David J.
• Nowak, Romana A.

• Hedgehog
• growth differentiation factor 9 (GDF9)
• Theca cell
• Lineage specification

Statement dc:rights

• Copyright 2015 Chang Liu

Handle dc:identifier

http://hdl.handle.net/2142/78577

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/78577