Journal article
Notch Signaling Regulates Ovarian Follicle Formation and Coordinates Follicular Growth
Molecular endocrinology (Baltimore, Md.), Vol.28(4), pp.499-511
04/01/2014
DOI: 10.1210/me.2013-1288
PMCID: PMC3968400
PMID: 24552588
Abstract
Ovarian follicles form through a process in which somatic pregranulosa cells encapsulate individual germ cells from germ cell syncytia. Complementary expression of the Notch ligand, Jagged1, in germ cells and the Notch receptor, Notch2, in pregranulosa cells suggests a role for Notch signaling in mediating cellular interactions during follicle assembly. Using a Notch reporter mouse, we demonstrate that Notch signaling is active within somatic cells of the embryonic ovary, and these cells undergo dramatic reorganization during follicle histogenesis. This coincides with a significant increase in the expression of the ligands, Jagged1 and Jagged2; the receptor, Notch2; and the target genes, Hes1 and Hey2. Histological examination of ovaries from mice with conditional deletion of Jagged1 within germ cells (J1 knockout [J1KO]) or Notch2 within granulosa cells (N2 knockout [N2KO]) reveals changes in follicle dynamics, including perturbations in the primordial follicle pool and antral follicle development. J1KO and N2KO ovaries also contain multioocytic follicles, which represent a failure to resolve germ cell syncytia, and follicles with enlarged oocytes but lacking somatic cell growth, signifying a potential role of Notch signaling in follicle activation and the coordination of follicle development. We also observed decreased cell proliferation and increased apoptosis in the somatic cells of both conditional knockout lines. As a consequence of these defects, J1KO female mice are subfertile; however, N2KO female mice remain fertile. This study demonstrates important functions for Jagged1 and Notch2 in the resolution of germ cell syncytia and the coordination of somatic and germ cell growth within follicles of the mouse ovary.
Details
- Title: Subtitle
- Notch Signaling Regulates Ovarian Follicle Formation and Coordinates Follicular Growth
- Creators
- Dallas A. Vanorny - Northwestern UniversityRexxi D. Prasasya - Northwestern UniversityAbha J. Chalpe - Northwestern UniversitySigne M. Kilen - Northwestern UniversityKelly E. Mayo - Northwestern University
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.28(4), pp.499-511
- Publisher
- Endocrine Soc
- DOI
- 10.1210/me.2013-1288
- PMID
- 24552588
- PMCID
- PMC3968400
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Number of pages
- 13
- Grant note
- T32 GM08061 / Cellular and Molecular Basis of Disease Training Program through National Institutes of Health, Institute of General Medical Sciences P30CA060553 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32GM008061 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P01HD021921 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P01 HD021921 / Eunice Kennedy Shriver National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P30NS054850 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) P30 NS054850 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 04/01/2014
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984702942602771
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