Elsevier

Developmental Biology

Volume 412, Issue 2, 15 April 2016, Pages 250-260
Developmental Biology

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

https://doi.org/10.1016/j.ydbio.2016.02.024Get rights and content
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Highlights

  • Supporting cells of medullary and cortical follicles derived from common precursors.

  • WNT/β-catenin and p27/FOXL2 differentially regulate supporting cell development.

  • WNT/β-catenin drive proliferation supporting cell self-renewal.

  • p27/FOXL2 mark mitotically arrested supporting cells.

  • Novel flow cytometric analysis of fetal ovarian development.

Abstract

Sexual development is initiated through differentiation of testicular Sertoli cells or ovarian granulosa cells. Although these supporting cells are considered to develop from common bipotential precursors, recent evidence suggests that distinct supporting cell populations are present in the ovary, with one providing granulosa cells of the medullary follicles and the other providing granulosa cells of the cortical follicles, the latter of which support lifelong fertility. Here, we demonstrate that XX fetal gonads contain GATA4 expressing supporting cells that either enter mitotic arrest, or remain proliferative. Blocking WNT signalling reduces XX supporting cell proliferation, while stabilising β-catenin signalling promotes proliferation, indicating that the renewal of pre-granulosa cells is dependent on WNT/β-catenin signalling in the proliferative supporting cell population. In contrast, XX supporting cells express p27 and FOXL2 and are maintained in mitotic arrest. Although FOXL2 is required for maintaining high levels of p27 expression, it is dispensable for entry and maintenance of mitotic arrest in XX supporting cells. Combined our data suggest that both medullary and cortical precursors arise from a common GATA4 expressing cell type. In addition, this work indicates that a balance between supporting cell self-renewal and differentiation is maintained in the developing ovary by relative WNT/β-catenin and p27/FOXL2 activities. This study provides significant new insights into the origin and formation of ovarian follicles and evidence supporting a common fetal origin of medullary and cortical granulosa cells.

Keywords

β-catenin
WNT4
FOXL2
Ovary
Granulosa
Follicle

Cited by (0)

1

Current address: Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

2

Current address: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.

3

These authors contributed equally to this paper.