The Genetics and Biology of FOXL2

Abstract

FOXL2 encodes a transcription factor that regulates a wide array of target genes including those involved in sex development, eyelid development, ovarian function and maintenance, genomic integrity as well as cellular pathways such as cell-cycle progression, proliferation, and apoptosis. The role of FOXL2 has been widely studied in humans and animals. Consistent with its role in ovarian and eyelid development, over 100 germline variants in FOXL2 are associated with blepharophimosis, ptosis, and epicanthus inversus syndrome in humans, an autosomal dominant condition characterised by ovarian dysgenesis/premature ovarian insufficiency, as well as defective eyelid development. Reflecting its role in apoptosis and proliferation, a somatic variant in FOXL2 causes adult granulosa cell tumours in humans. Despite being widely studied and having clear relevance to human disease, much remains unknown about the genes FOXL2 regulates and how it exerts its wide-reaching effect on multiple organs. This review focuses on FOXL2 and its varied roles as a transcription factor in sex determination, ovarian maintenance and function, eyelid development, genome integrity, and cell regulation, followed by discussion of the in vivo disruption of FOXL2 in humans and other species.

Keywords: Blepharophimosis, ptosis, and epicanthus inversus syndrome; FOXL2; Ovarian development; Premature ovarian insufficiency.