The sex of an individual is determined by the fate of the gonad. While the expression of Sry and Sox9 is sufficient to induce male development, we here show that female differentiation requires activation of the canonical beta-catenin signaling pathway. beta-catenin activation is controlled by Rspo1 in XX gonads and Rspo1 knockout mice show masculinized gonads. Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis. Moreover, germ cells of XX knockout embryos show changes in cellular adhesions and a failure to enter XX specific meiosis. Sex cords develop around birth, when Sox9 becomes strongly activated. Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development.

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddn016DOI Listing

Publication Analysis

Top Keywords

beta-catenin signaling
12
fate gonad
8
canonical beta-catenin
8
beta-catenin activation
8
activation
5
activation beta-catenin
4
rspo1
4
signaling rspo1
4
rspo1 controls
4
controls differentiation
4

Similar Publications

Purpose: We aimed to explore the mechanism by which Boron-doped nano-hydroxyapatite (B-nHAp) facilitates the proliferation and differentiation of osteoblasts through controlled release of B.

Methods: B-nHAp characterization was accomplished by means of X-ray diffraction, scanning electron microscopy, inductively coupled plasma mass spectrometry, and transmission electron microscopy. Human bone marrow mesenchymal stem cells (hBMSCs) were subjected to flow cytometry, alizarin red S staining, and cell counting kit-8 assay for proliferation and differentiation determination.

View Article and Find Full Text PDF

Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation.

Stem Cell Reports

December 2024

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address:

During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs).

View Article and Find Full Text PDF

The molecule events expression of TGF-β/Smad signaling pathway in morphological and structural developmental characteristics of gonads in goose embryos.

Poult Sci

January 2025

College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China; Key Laboratory of Animal Production, Product Quality and Security, Jilin Agricultural University, Ministry of Education, Changchun, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address:

China is the largest producer and consumer of geese with significant social and economic value in agriculture. The Jilin White Goose, known for its excellent egg-laying and reproductive characteristics, is a prominent breeding breed in the northeast of China widely used for cross-breeding.Gonad development is a complex process, which will differentiate into testes or ovaries, thus affecting sex determination.

View Article and Find Full Text PDF

Gestational diabetes mellitus (GDM), defined as glucose intolerance occurring or first detected during pregnancy, affects approximately 8% of pregnancies worldwide. The dysfunction of trophoblasts in pregnancies complicated by GDM is associated with changes in trophoblast cell functions, resulting in compromised proliferation and regulation of the cell cycle. Cyclin B1 (CCNB1), a pivotal controller of the start of mitosis, is crucial in these mechanisms.

View Article and Find Full Text PDF

LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.

Cancer Metastasis Rev

January 2025

Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, 5005, Australia.

Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!