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Class Set of Slides (Somatic Sex Reprogramming)

Class Set of Slides (Somatic Sex Reprogramming) - Somatic...

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Unformatted text preview: Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation Jovian W., Jamey G. & Aliya S. Outline • Introduction ▫ Gonad & Cellular Differentiation ▫ Transcription Factors ▫ Signaling Pathways • Methods/Results ▫ Reprogramming of Granulosa to Sertoli Like Cells ▫ Testosterone Producing Leydig like Cell by loss of FOXL2 • Discussion ▫ Insert Subtopics • Conclusion What defines a male? What defines a female? http://graphics.cs.cmu.edu/courses/15- 463/2004_fall/www/handins/eryu/final/ http://graphics.cs.cmu.edu/courses/15- 463/2004_fall/www/handins/eryu/final/ What Infleunces Sex Determination? • Sex Chromosomes ▫ XX : Female ▫ XY : Male • Genetic Cascade ▫ Gene expression key determinant ▫ Transcription factors ▫ X versus Y influences • Hormones ▫ Formation of secondary characteristics ▫ Males Testosterone Follicular Growth Factor 4 Prostaglandin ▫ Females Estrogen Progesterone • Environment Male Development • SRY switches testes development cascade ON • SRY in combination with FGF9 and PTGSD induce upregulation of SOX9 • SOX9 induces male gondal cell differentiation: ▫ Sertoli Cell ▫ Leydig Cells ▫ Mature male cells never enter apoptosis Female Development • Wnt4 and RSPO1 are expressed activating the female development pathway • Stabilization of β-catenin ▫ Ectopic expression of β-catenin (XY females) • Stabilized β-catenin trigger male pathway repressors ▫ FOXL2, DAX1 (SF1), ESR1/2 • Repressors bind to TESCO inhibiting SOX9 production • Formation of ovary and related cells: ▫ Theca ▫ Granulosa Undifferentiate d Gonads Wnt4 RSPO1 SRY β-catenin SOX9 Ovar y Teste s FOXL2 DAX1 (SF1 ) Gonad Cellular Development • Cell fate is determined once gender correct TF’s are allowed to be expressed Granulosa Theca Leydig Sertoli Mutations ctopic duplication of SOX 9 in a fetus can lead to XX males nt4 and RSPO1 • Loss of function mutations • Partial male sex reversal of XX gonads AX1 Overexpression • Sex-reversal in XY males lobal deletion of FOXL2 during development • Ovary dysgenesis • Infertility • Activation of some testis specific genes Purpose of the Study • Determine what happens when mutations arise that prevent the repression of SOX9 in ADULT female mice: ▫ Changes to sex differentiation pathway Loss of FOXL 2 and ESR1/2 receptor ▫ Ovary plasticity ▫ Reprogramming of cell fates The Problem • Are mutations leading to the formation of leydig and sertoli like...
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Class Set of Slides (Somatic Sex Reprogramming) - Somatic...

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