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FOXL2 interaction with different binding partners regulates the dynamics of ovarian development
Roberta Migale1, Michelle Neumann1, Richard Mitter2
1Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London NW1 1AT, UK.
Science Advances
|March 22, 2024
Summary
The transcription factor FOXL2 is crucial for female fertility, with distinct roles during ovarian development. Its interaction with USP7 is vital for somatic cell differentiation and germ cell development, impacting fertility.
Area of Science:
- Reproductive biology
- Developmental biology
- Genetics
Background:
- The transcription factor FOXL2 is essential for female fertility in ovarian somatic cells.
- Differentiation timing of FOXL2 deletion impacts ovarian development, suggesting stage-specific functions.
Purpose of the Study:
- To comprehensively investigate the role of FOXL2 in ovarian development using a multi-omics approach.
- To identify FOXL2 targets and interacting partners in somatic cells throughout ovarian development.
Main Methods:
- Multi-omics analysis including gene expression and chromatin accessibility.
- Genome-wide identification of FOXL2 targets and interacting proteins.
- Functional studies involving gene deletion, including ubiquitin-specific protease 7 (Usp7).
Main Results:
- FOXL2 regulates a greater number of targets postnatally, influencing primordial follicle formation and steroidogenesis.
- FOXL2 interacts with key factors, including USP7, in regulating ovarian somatic cell functions.
- Deletion of Usp7 impairs somatic cell differentiation, germ cell nest breakdown, and leads to sterility.
Conclusions:
- FOXL2 plays critical, stage-specific roles in ovarian development and female fertility.
- The interaction of FOXL2 with factors like USP7 is essential for normal ovarian morphogenesis and function.
- This study provides a valuable resource for understanding female infertility causes.
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