WNT/β-catenin and p27/FOXL2 differentially regulate supporting cell proliferation in the developing ovary

Area of Science:

• Reproductive biology
• Developmental biology
• Cell biology

Background:

• Sexual development relies on Sertoli (testicular) or granulosa (ovarian) cell differentiation.
• Ovarian supporting cells may originate from distinct precursors for medullary and cortical follicles.
• Cortical follicle precursors support lifelong fertility.

Purpose of the Study:

• Investigate the origin and differentiation of ovarian supporting cells in XX fetuses.
• Determine the signaling pathways regulating supporting cell proliferation and mitotic arrest.
• Clarify the common fetal origin of medullary and cortical granulosa cells.

Main Methods:

• Analysis of GATA4 expressing cells in XX fetal gonads.
• Manipulation of WNT/β-catenin signaling to assess proliferation.
• Examination of p27 and FOXL2 expression in XX supporting cells.
• Assessment of FOXL2's role in mitotic arrest.

Main Results:

• XX fetal gonads contain GATA4+ supporting cells that either proliferate or enter mitotic arrest.
• WNT/β-catenin signaling promotes supporting cell proliferation; blocking it reduces proliferation.
• XX supporting cells express p27 and FOXL2, maintaining mitotic arrest.
• FOXL2 is necessary for high p27 levels but not for mitotic arrest entry/maintenance.

Conclusions:

• Medullary and cortical ovarian follicle precursors likely arise from a common GATA4+ cell type.
• Ovarian development balances supporting cell self-renewal and differentiation via WNT/β-catenin and p27/FOXL2 pathways.
• This study offers insights into ovarian follicle formation and a common fetal origin for granulosa cells.