Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells

Liu, Chang; Jia, Peng; Matzuk, Martin M.; Yao, Hisayuki

doi:10.1038/ncomms7934

Cited by 181 publications

(181 citation statements)

References 39 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…Other cells, such as the precursors of the steroidogenic cells, may also be an origin. Theca cells were recently reported to be derived from Wt1-positive cells indigenous to the ovary and Gli1-positive mesenchymal cells that have migrated from the mesonephros (Liu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Leydig cells first appear in testes at E12.5, whereas theca-interstitial cells are observed postnatally in the ovaries along with the development of ovarian follicles. The origins of Leydig cells (Weaver et al, 2009;Barsoum and Yao, 2010;DeFalco et al, 2011) and theca cells (Liu et al, 2015) have been studied previously. However, the underlying mechanism that regulates the differentiation between supporting cells and steroidogenic cells during gonad development is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression

et al. 2016

View full text Add to dashboard Cite

Supporting cells (Sertoli and granulosa) and steroidogenic cells (Leydig and theca-interstitium) are two major somatic cell types in mammalian gonads, but the mechanisms that control their differentiation during gonad development remain elusive. In this study, we found that deletion of Wt1 in the ovary after sex determination caused ectopic development of steroidogenic cells at the embryonic stage. Furthermore, differentiation of both Sertoli and granulosa cells was blocked when Wt1 was deleted before sex determination and most genital ridge somatic cells differentiated into steroidogenic cells in both male and female gonads. Further studies revealed that WT1 repressed Sf1 expression by directly binding to the Sf1 promoter region, and the repressive function was completely abolished when WT1 binding sites were mutated. This study demonstrates that Wt1 is required for the lineage specification of both Sertoli and granulosa cells by repressing Sf1 expression. Without Wt1, the expression of Sf1 was upregulated and the somatic cells differentiated into steroidogenic cells instead of supporting cells. Our study uncovers a novel mechanism of somatic cell differentiation during gonad development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The dose (1 mg/mouse) and frequency (one injection) of the tamoxifen treatment induced recombination for ∼24 h, so that all tdTomato-positive cells are derived specifically from the WT1 + cell population between E10.5 and E11.5 (Liu et al, 2015). At E11.5, or 24 h after tamoxifen treatment, the lineagelabeled Wt1…”

Section: T2mentioning

confidence: 99%

“…The cDNA preparation was synthesized using random hexamers and the Superscript II cDNA synthesis system (Invitrogen) following manufacturer's instruction. Gene expression was analyzed by real-time PCR using the Bio-Rad CFX96 Real-Time PCR Detection system (Liu et al, 2015). Taqman probes (ThermoFisher Scientific), were used to examine the fold changes of the transcripts.…”

Section: Gene Expression Analysismentioning

confidence: 99%

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

2016

Self Cite

View full text Add to dashboard Cite

Testis morphogenesis is a highly orchestrated process involving lineage determination of male germ cells and somatic cell types. Although the origin and differentiation of germ cells are known, the developmental course specific for each somatic cell lineage has not been clearly defined. Here, we construct a comprehensive map of somatic cell lineage progression in the mouse testis. Both supporting and interstitial cell lineages arise from WT1 + somatic progenitor pools in the gonadal primordium. A subpopulation of WT1 + progenitor cells acquire SOX9 expression and become Sertoli cells that form testis cords, whereas the remaining WT1 + cells contribute to progenitor cells in the testis interstitium. Interstitial progenitor cells diversify through the acquisition of HES1, an indication of Notch activation, at the onset of sex determination. HES1 + interstitial progenitors, through the action of Sertoli cell-derived Hedgehog signals, become positive for GLI1. The GLI1 + interstitial cells eventually develop into two cell lineages: steroid-producing fetal Leydig cells and non-steroidogenic cells. The fetal Leydig cell population is restricted by Notch2 signaling from the neighboring somatic cells. The non-steroidogenic progenitor cells retain their undifferentiated state during fetal stage and become adult Leydig cells in post-pubertal testis. These results provide the first lineage progression map that illustrates the sequential establishment of somatic cell populations during testis morphogenesis.

show abstract

“…The assembly of the follicles is completed by the recruitment of steroidogenic precursor cells to differentiate into theca cells [Hirshfield, 1991]. Recently, it has been shown that there are 2 sources of theca cell precursors: mesenchymal cells that reside within the ovary and a second population that migrates into the ovary from the mesonephros [Liu et al, 2015].…”

Section: Ovarian Developmentmentioning

confidence: 99%

Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development

Windley

Wilhelm

2015

Sex Dev

View full text Add to dashboard Cite

The development of any organ system requires a complex interplay of cellular signals to initiate the differentiation and development of the heterogeneous cell and tissue types required to carry out the organs' functions. In this way, an extracellular stimulus is transmitted to an intracellular target through an array of interacting protein intermediaries, ultimately enabling the target cell to elicit a response. Surprisingly, only a small number of signaling pathways are implicated throughout embryogenesis and are used over and over again. Gonadogenesis is a unique process in that 2 morphologically distinct organs, the testes and ovaries, arise from a common precursor, the bipotential genital ridge. Accordingly, most of the signaling pathways observed throughout embryogenesis also have been shown to be important for mammalian sex determination and gonad development. Here, we review the mechanisms of signal transduction within these pathways and the importance of these pathways throughout mammalian gonad development, mainly concentrating on data obtained in mouse but including other species where appropriate.

show abstract

Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells

Cited by 181 publications

References 39 publications

Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression

Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development

Contact Info

Product

Resources

About