FOXL2: at the crossroads of female sex determination and ovarian function

Adv Exp Med Biol. 2009:665:207-26. doi: 10.1007/978-1-4419-1599-3_16.

Abstract

The gene FOXL2 encodes a forkhead transcription factor whose mutations are responsible for the blepharophimosis ptosis epicanthus-inversus syndrome. This genetic disorder is characterized by eyelid and mild craniofacial abnormalities often in association with premature ovarian failure. FOXL2 orthologs are found throughout the animal phylum and its sequence is highly conserved in vertebrates. FOXL2 is one of the earliest ovarian markers and it offers, alongwith its targets, a model to study ovarian development and function. In this chapter, we review recent data concemingits mutations, targets, regulation and functions. Studies of the cellular consequences of FOXL2 mutations seem to indicate that aggregation is a common pathogenic mechanism. However, no reliable genotype/phenotype correlation has been established to predict the exact impact of point mutations in the coding region of FOXL2. FOXL2 has been suggested to be involved in the regulation of cholesterol homeostasis, steroid metabolism, apoptosis, reactive oxygen species detoxification and inflammation processes. Interestingly, all these processes are not equally affected by FOXL2 mutations. The elucidation of the impact of the FOXL2 function in the ovary will allow a better understanding of normal ovarian development and function as well as the pathogenic mechanisms underlying BPES.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Female
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / physiology*
  • Humans
  • Ovary / physiology*
  • Sex Determination Processes*

Substances

  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors