A New Constitutive Foxl2-Cre Mouse Model Reveals Foxl2 -Derived Cell Fate in Reproductive and Non-Reproductive Tissues
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ID: 315698
2026
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Abstract
FOXL2 is a highly conserved transcription factor that is essential for ovarian development and female fertility. In humans, FOXL2 mutations or deletions cause Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) leading to eyelid defects and, in BPES type I, primary ovarian insufficiency. BPES is also associated with a wide range of less common phenotypes such as craniofacial features, cleft palate, or heart defects. In this study, we generated a new constitutive Foxl2-Cre mouse model using CRISPR/Cas9 editing. Crossing Foxl2-Cre mice with Rosa-tdTomato reporter confirmed robust and specific labeling of FOXL2+ cells during fetal development. We provide a detailed characterization of the permanent labeling of cells that, at any time in development, expressed Foxl2, with a particular interest on organs associated with a spectrum of features identified in BPES patients. Our model effectively targeted key reproductive tissues, such as fetal ovarian somatic cells, including granulosa, interstitium and theca-cell precursors, the anterior pituitary, and mesenchymal cells of the uterus and oviduct. We also identified Foxl2-derived cells in the supporting-like cells of the testis, as well as in the peri-urethral cells of the external genitalia. Beyond the reproductive organs, Foxl2-derived cells were identified in several other tissues relevant to BPES, including the head, palate and the outflow tract of the heart. Overall, this Foxl2-Cre model provides a new tool for reproductive organ studies, and our characterization of Foxl2-derived cell fate brings a new perspective into the potential roles of FOXL2 in the wide spectrum of clinical features associated with BPES.
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| Authors | Barbara Nicol, Artiom Gruzdev, Ciro Amato, Chang Liu, Gregory J Scott, Thomas B Hagler, Manas K. Ray, Humphrey Hung-Chang Yao |
| Journal | biology of reproduction |
| Year | 2026 |
| DOI |
10.1093/biolre/ioag116
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| URL | |
| Keywords | Keywords not found |
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