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Updated: Jul 12, 2025

Inducible and Reversible Dominant-negative DN Protein Inhibition
Published on: January 7, 2019
[Loss of RBFOX2 inhibits meiotic initiation in male mice]
Lin Yan1,2, Jian Chen2,3, Yan Ning2,3,4
1Institute of Material Science and Information Technology, Anhui University, Hefei 230601, Anhui, China.
Abstract:
Meiotic initiation is a critical step in gametogenesis. Recently, some genes required for meiotic initiation have been identified. However, meiosis-initiating factors and the underlying mechanisms are far from being fully understood. We have established a long-term culture system of spermatogonial stem cells (SSCs) and an in vitro model of meiotic initiation using mouse SSCs. Our previous study revealed that the RNA-binding protein RBFOX2 may regulate meiotic initiation, but the role and the mechanism need to be further elucidated. In this study, we constructed RBFOX2 knockdown SSC lines by using lentivirus-mediated gene delivery method, and found that the knockdown SSCs underwent normal self-renewal, mitosis and differentiation. However, they were unable to initiate meiosis when treated with retinoic acid, and they underwent apoptosis. These results indicate that RBFOX2 plays an essential role in meiotic initiation of spermatogonia. This work provides new clues for understanding the functions of RNA-binding proteins in meiotic initiation.
Insights
RNA binding protein RBFOX2 is essential for initiating meiosis in mouse spermatogonial stem cells (SSCs). Knockdown SSCs fail to initiate meiosis and undergo apoptosis, highlighting RBFOX2
Area of Science:
- Reproductive Biology
- Molecular Genetics
- Cell Biology
Context:
- Meiotic initiation is crucial for gametogenesis but its regulatory factors remain unclear.
- Spermatogonial stem cells (SSCs) and an in vitro model of meiotic initiation were established.
- The RNA-binding protein RBFOX2 was previously suggested to regulate meiotic initiation.
Purpose:
- To investigate the specific role and mechanism of RBFOX2 in meiotic initiation.
- To determine the consequences of RBFOX2 deficiency in SSCs during meiosis induction.
Summary:
- RBFOX2 knockdown SSC lines were created using lentivirus-mediated gene delivery.
- Knockdown SSCs maintained self-renewal, mitosis, and differentiation but failed to initiate meiosis upon retinoic acid treatment.
- RBFOX2-deficient SSCs exhibited apoptosis when meiosis induction was attempted.
Impact:
- RBFOX2 is demonstrated to be essential for initiating meiosis in spermatogonia.
- This study provides novel insights into the function of RNA-binding proteins in the complex process of meiotic initiation.
- Findings contribute to a deeper understanding of male gametogenesis regulation.
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