Forkhead box protein E3 (FOXE3) also known as forkhead-related transcription factor 8 (FREAC-8) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''FOXE3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
located on the short arm of chromosome 1.
Function
FOXE3 is a
forkhead-box transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
which is involved in the proper formation of the ocular lens and is post-natally expressed in the lens epithelium.
Development
Foxe3, also known as Forkhead Box E3, is a transcription factor that is responsible for the formation of the lens placode, a precursor to the lens of the eye, and the lens itself. Foxe3 controls multiple processes during development of the lens including, the expression of Cryaα which controls the solubility of the crystalline protein complex in the developing lens. Reduced solubility can lead to potential cataract formation due to crystallization of the lens. Foxe3 also controls the regulation of Prox1, which is responsible for cell cycle progression. As Foxe3 expression downregulates, Prox1 expression increases causing a reduction in cellular proliferation in the anterior lens. Foxe3 also regulates platelet-derived growth factor receptor-α (Pdgfrα) expression. This is responsible for lens fiber differentiation within the epithelium of certain parts of the lens. There are multiple defects associated with dysfunction of this gene with most being classified under the term anterior segment dysgenesis (ASD). For example, Peters anomaly is a rare disorder obtained during development characterized by adhesions due to malformations of the posterior corneal stroma, the absence of Descemet's membrane and the corneal endothelium, and corneal opacities. This syndrome can be attributed to fetal alcohol syndrome and aneuploidy. Scientists have generated a knockout model for Foxe3 in mice and are testing the effects on the lenses of those animals. So far, it appears that Foxe3 is essential for normal lens development.
Clinical significance
Mutations in the FOXE3 gene are associated with
anterior segment mesenchymal dysgenesis
Anterior segment mesenchymal dysgenesis, or simply anterior segment dysgenesis (ASD), is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, ...
.
Homozygous mutations in this gene have been associated with a number of ocular diseases such as congenital
aphakia
Aphakia is the absence of the lens of the eye, due to surgical removal, such as in cataract surgery, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, high degree of farsightedness ( hyperopia), and a de ...
,
,
microphthalmia
Microphthalmia (Greek: grc, μικρός, mikros, small, label=none, grc, ὀφθαλμός, ophthalmos, eye, label=none, also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both ( ...
, and optic disc
coloboma
A coloboma (from the Greek , meaning defect) is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is presen ...
.
There have also been reports of heterozygous mutations causing less severe ocular diseases such as anterior segment dysgenesis (sometimes referred to as anterior segment mesenchymal dysgenesis),
and Peter's anomaly.
See also
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FOX proteins
FOX (forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic ...
References
Further reading
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Forkhead transcription factors
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