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SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation
Elanor N Wainwright1, Joan S Jorgensen, Youngha Kim
1Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Biology of Reproduction
|July 12, 2013
Summary
MicroRNAs miR-202-5p/3p are crucial for male fetal gonad development. Their expression is regulated by SOX9, a key testis-determining factor, indicating an early role in testis differentiation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- MicroRNAs regulate gene expression during development, but their specific roles in fetal gonad differentiation remain unclear.
- Understanding the molecular mechanisms of gonad development is crucial for reproductive health.
Purpose of the Study:
- To investigate the role of conserved microRNAs, specifically miR-202-5p and miR-202-3p, in mouse embryonic gonad differentiation.
- To determine the regulatory relationship between miR-202 and key sex-determining factors like SOX9 and SF1.
Main Methods:
- Analysis of miR-202 expression patterns in developing mouse gonads.
- In vivo studies involving ectopic expression of pri-miR-202 in XX gonads.
- Utilizing a conditional Sox9-null mouse model to assess pri-miR-202 transcription.
- Ex vivo promoter assays to identify regulatory elements and transcription factor binding sites (SOX9, SF1).
Main Results:
- miR-202-5p and miR-202-3p are expressed in a sexually dimorphic pattern during testis differentiation, primarily in Sertoli cells.
- Ectopic expression of pri-miR-202 in XX gonads did not alter ovarian development pathways.
- Pri-miR-202 transcription is dependent on SOX9, with reduced expression in Sox9-null XY gonads.
- The pri-miR-202 promoter is activated by SOX9 and SF1, suggesting it is a direct transcriptional target.
Conclusions:
- The conserved microRNAs miR-202-5p/3p play a significant role in early testis development.
- miR-202 expression is regulated downstream of the testis-determining factor SOX9, highlighting its integration into the male sex determination pathway.
Keywords:
microRNAsmouse gonad developmenttestis differentiationtranscriptional regulationtransgenic miceMore Related Videos
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