News | Key Proteins in Mouse Ovary Development Identified
Researchers at the Francis Crick Institute recently identified proteins that regulate ovary development in mice. The discovery may deepen understanding of how female infertility develops.
In earlier research, scientists identified key genes that initiate ovarian development in mouse embryos. The new study sought to understand which genes maintain ovarian function after birth, including egg production.
The key role of the FOXL2 gene
Previous experiments showed that removing the FOXL2 gene at different stages of development has different effects. Removing it during embryonic development causes abnormal ovarian development and infertility in adult mice. Removing it in adult mice causes the ovaries to begin developing testicular characteristics.
In the newly published study, the team found that although FOXL2 acts during embryonic development, its effects are more pronounced after birth, when it regulates the activity of many key genes, including genes involved in egg development.
New findings on the USP7 protein
FOXL2 is a protein that binds to specific regions of DNA called enhancers and affects the expression of other genes. Researchers used a technique called chromatin proteomics to identify all proteins that bind to FOXL2 and found a marked increase in FOXL2 protein interactions in the ovaries after birth.
Among their findings, they identified a protein called USP7 that binds to DNA together with FOXL2. Researchers had not previously identified an interaction between USP7 and FOXL2 or a role for USP7 in ovarian development.
When researchers removed the Usp7 gene in mice, the mice failed to develop normal ovaries after puberty and became infertile. The team believes USP7 may be needed to stabilize FOXL2's position on DNA.
Implications for humans
FOXL2 and USP7 have similar roles in humans. People who lack one copy of the FOXL2 gene can produce eggs, but their ovaries do not fully develop, leading to fertility problems. USP7 mutations can also cause infertility and neurodevelopmental disorders.
Future research
Robin Lovell-Badge, Group Leader of the Stem Cell Biology and Developmental Genetics Laboratory at the Francis Crick Institute, said, "Our research advances two key questions—what drives ovarian development and how ovarian function is maintained. We found that FOXL2 has very different roles throughout development and identified another key protein, USP7."
This study is the first to use these methods to observe interactions between FOXL2 and other proteins as they bind to DNA in mouse ovaries. The identification of USP7 through this approach may guide the future discovery of additional proteins responsible for ovarian development.
Researchers will continue studying the role of USP7 in sexual development.
News | Key Proteins in Mouse Ovary Development Identified
News | Key Proteins in Mouse Ovary Development Identified
Researchers at the Francis Crick Institute recently identified proteins that regulate ovary development in mice. The discovery may deepen understanding of how female infertility develops.
In earlier research, scientists identified key genes that initiate ovarian development in mouse embryos. The new study sought to understand which genes maintain ovarian function after birth, including egg production.
The key role of the FOXL2 gene
Previous experiments showed that removing the FOXL2 gene at different stages of development has different effects. Removing it during embryonic development causes abnormal ovarian development and infertility in adult mice. Removing it in adult mice causes the ovaries to begin developing testicular characteristics.
In the newly published study, the team found that although FOXL2 acts during embryonic development, its effects are more pronounced after birth, when it regulates the activity of many key genes, including genes involved in egg development.
New findings on the USP7 protein
FOXL2 is a protein that binds to specific regions of DNA called enhancers and affects the expression of other genes. Researchers used a technique called chromatin proteomics to identify all proteins that bind to FOXL2 and found a marked increase in FOXL2 protein interactions in the ovaries after birth.
Among their findings, they identified a protein called USP7 that binds to DNA together with FOXL2. Researchers had not previously identified an interaction between USP7 and FOXL2 or a role for USP7 in ovarian development.
When researchers removed the Usp7 gene in mice, the mice failed to develop normal ovaries after puberty and became infertile. The team believes USP7 may be needed to stabilize FOXL2's position on DNA.
Implications for humans
FOXL2 and USP7 have similar roles in humans. People who lack one copy of the FOXL2 gene can produce eggs, but their ovaries do not fully develop, leading to fertility problems. USP7 mutations can also cause infertility and neurodevelopmental disorders.
Future research
Robin Lovell-Badge, Group Leader of the Stem Cell Biology and Developmental Genetics Laboratory at the Francis Crick Institute, said, "Our research advances two key questions—what drives ovarian development and how ovarian function is maintained. We found that FOXL2 has very different roles throughout development and identified another key protein, USP7."
This study is the first to use these methods to observe interactions between FOXL2 and other proteins as they bind to DNA in mouse ovaries. The identification of USP7 through this approach may guide the future discovery of additional proteins responsible for ovarian development.
Researchers will continue studying the role of USP7 in sexual development.
Source:
Collected online