The role of WNT signaling in adult ovarian folliculogenesis

Wingless-type mouse mammary tumor virus integration site (WNT) signaling molecules are locally secreted glycoproteins that play important role in regulation of ovarian follicle maturation and steroid production. Components of the WNT signaling pathway have been demonstrated to impact reproductive functions, including embryonic development of the sex organs and regulation of follicle maturation controlling steroidogenesis in the postnatal ovary. Emerging evidence underscores the complexity of WNT signaling molecules in regulation of dynamic changes that occur in the ovary during the reproductive cycle. While disruption in the WNT signaling cascade has been recognized to have deleterious consequences to normal sexual development, more recent studies are beginning to highlight the importance of these molecules in adult ovarian function related to follicle development, corpus luteum formation, steroid production and fertility. Hormonal regulation of WNT genes and expression of members of the WNT signaling network, including WNT ligands, frizzled receptors, and downstream signaling components that are expressed in the postnatal ovary at distinct stages of the estrous cycle suggest a crucial role in normal ovarian function. Similarly, FSH stimulation of T-cell factor-dependent gene expression requires input from β-catenin, a lynchpin molecule in canonical WNT signaling, further indicating β-catenin participation in regulation of follicle maturation. This review will focus on the multiple functions of WNT signaling in folliculogenesis in the adult ovary.

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Developmental Biology II: The Role of WNT Signaling in Bone Regeneration

10.2310/ps.10122 ◽

2019 ◽

Author(s):

Mimi R. Borrelli ◽

Ledibabari M. Ngaage ◽

Derrick C. Wan ◽

Michael T. Longaker ◽

H. Peter Lorenz

Keyword(s):

Wnt Signaling ◽

Bone Regeneration ◽

Bone Development ◽

Integration Site ◽

Wnt Signaling Pathway ◽

Cell Proliferation And Differentiation ◽

Important Regulator ◽

Cell Niche ◽

Canonical Wnt

Wingless-related integration site (Wnt) signaling is an important regulator of bone development and regeneration. Wnts are short-range signaling molecules which act within the skeletal stem cell niche to influence cell proliferation and differentiation. Nineteen different Wnts have been identified in humans. Disruptions to Wnt signaling can lead to impairments in bone healing. Recent work has elucidated the complexities of Wnt signaling during bone development, repair, and regeneration, and highlighted its value as a potential therapeutic target for tissue regeneration. Here, we discuss the role of the canonical-Wnt-signaling pathway, its regulatory role in bone regeneration, and the recent clinical advance made towards its manipulation in regenerative medicine. This review contains 3 figures and 50 references. Keywords: osteogenesis, bone regeneration, bone remodeling, endochondral ossification, osteoblast, osteoprogenitor, lithium, fracture healing

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Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation

International Journal of Molecular Sciences ◽

10.3390/ijms21155495 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5495

Author(s):

Lai-Sheung Chan ◽

Hong-Lok Lung ◽

Roger Kai-Cheong Ngan ◽

Anne Wing-Mui Lee ◽

Sai Wah Tsao ◽

...

Keyword(s):

Cell Migration ◽

Nasopharyngeal Carcinoma ◽

Wnt Signaling ◽

Signaling Pathways ◽

Integration Site ◽

Wnt Signaling Pathway ◽

Luciferase Reporter ◽

Loss Of Function ◽

Tumor Sphere ◽

Sphere Formation

The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.

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WOMEN IN REPRODUCTIVE SCIENCE: Lessons from bioengineering the ovarian follicle: a personal perspective

Reproduction ◽

10.1530/rep-19-0190 ◽

2019 ◽

Vol 158 (6) ◽

pp. F113-F126 ◽

Cited By ~ 1

Author(s):

Teresa K Woodruff

Keyword(s):

Reproductive Tract ◽

Materials Science ◽

Ovarian Function ◽

Ovarian Follicle ◽

Model Systems ◽

Personal Perspective ◽

The Past ◽

Reproductive Science ◽

Follicle Maturation

The ovarian follicle and its maturation captivated my imagination and inspired my scientific journey – what we know now about this remarkable structure is captured in this invited review. In the past decade, our knowledge of the ovarian follicle expanded dramatically as cross-disciplinary collaborations brought new perspectives to bear, ultimately leading to the development of extragonadal follicles as model systems with significant clinical implications. Follicle maturation in vitro in an ‘artificial’ ovary became possible by learning what the follicle is fundamentally and autonomously capable of – which turns out to be quite a lot. Progress in understanding and harnessing follicle biology has been aided by engineers and materials scientists who created hardware that enables tissue function for extended periods of time. The EVATAR system supports extracorporeal ovarian function in an engineered environment that mimics the endocrine environment of the reproductive tract. Finally, applying the tools of inorganic chemistry, we discovered that oocytes require zinc to mature over time – a truly new aspect of follicle biology with no antecedent other than the presence of zinc in sperm. Drawing on the tools and ideas from the fields of bioengineering, materials science and chemistry unlocked follicle biology in ways that we could not have known or even predicted. Similarly, how today’s basic science discoveries regarding ovarian follicle maturation are translated to improve the experience of tomorrow’s patients is yet to be determined.

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The Presence of Wnt Signaling Mutations in Patients With Diabetic Retinopathy

Journal of VitreoRetinal Diseases ◽

10.1177/2474126419868889 ◽

2019 ◽

Vol 4 (1) ◽

pp. 28-35

Author(s):

Omar Moinuddin ◽

Prethy Rao ◽

Edward H. Wood ◽

Maxwell S. Stem ◽

Kimberly A. Drenser ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Genetic Testing ◽

Wnt Signaling ◽

Signaling Pathway ◽

Integration Site ◽

Wnt Signaling Pathway ◽

Case Review ◽

Hba1c Control

Purpose: The relationship between poor hemoglobin A1c (HbA1c) control and risk of proliferative diabetic retinopathy (PDR) is well known. Nevertheless, some patients have discordant disease (controlled HbA1c and severe PDR or vice versa). One potential explanation for this discrepancy is the presence of underlying genetic mutations in the Wingless-related integration site (Wnt) signaling pathway. However, minimal clinical data exist on the presence of Wnt signaling mutations in patients with diabetes mellitus (DM) and the correlation with diabetic retinopathy. Methods: Retrospective, nonconsecutive case review of patients with type 1 or 2 DM who underwent genetic testing for at least 1 recognized Wnt signaling pathway mutation from 2011 to 2016. The clinical course and retinal images were reviewed for patients with identifiable mutations. Results: Thirty-six patients, ages 13 to 79 years, consented for genetic analysis. Three patients (8.3%) exhibited at least 1 recognized genetic mutation in the Wnt signaling pathway. Case 1 was a 65-year-old female with type 1 diabetes for > 20 years, HbA1c <7.0%, and no findings of diabetic retinopathy (Tetraspanin 12). Case 2 was a 13-year-old male with type 1 diabetes for 8 years, moderate HbA1c control (7.6-8.3%), and absence of diabetic retinopathy (Norrin). Case 3 was a 48-year-old male with severe PDR requiring multiple laser and antivascular endothelial growth factor (anti-VEGF) treatments despite well-controlled HbA1c (6.0%) (Frizzled-4). Conclusion: Wnt signaling pathway mutations exist in patients with DM. Further studies investigating the prevalence and clinical significance of these mutations in a larger diabetic population are warranted. Identification of these patients with genetic testing may enable earlier medical intervention.

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