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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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The Pax6 gene was first defined by homology to Drosophila gene paired as a member of the vertebrate paired box-containing (PAX) family[1]. Located on chromosome 11p13, it encodes a 422-amino-acid transcription factor, occupying 14 exons in a 22 kb genomic region[2]. Pax6 contains an amino terminal paired domain (PD), a glycine-rich hinge region (Gln/Gly), a homeodomain (HD) and a carboxy terminal Proline/Serine/Threonine (PST) rich transactivation domain[3]. Pax6 is highly conserved across vertebrates and invertebrates[4]. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene; Pax6 (5a) isoform is made by alternatively splicing exon 5a; inclusion of this 14 amino acid coding region changes the binding activity of protein, and leads to different biological activities[5]. The human peptide encoded by exon 5a differs by a single amino acid from the corresponding mouse and zebrafish peptides [2].

Pax6 is expressed in the developing eye, adult retina, lens and cornea, developing telencephalon, thalamus, pituitary, pineal, cerebellum, spinal cord and pancreas [6]. It is best known for its role as a master regulator of eye development [7] [8][9][10][11][12][5][13]; studies have also shown it plays substantial role in brain [14][15][16][17]; pancreatic [18][19] and pituitary development [20][21]. Though human and mouse Pax6 share exact amino acid sequence, Pax6 is shown to play different roles in brain development in two species; it functions as a master regulator of early specification of the neuroectoderm in human, but it is not expressed until later stages of neural stem cell development in mice [17].

As a transcription factor involved in different tissue developments, Pax6 regulates the expression of a wide range of molecules, including transcription factors, cell adhesion and signalling molecules, hormones and structural proteins [22]. In turn, Pax6 expression is regulated by upstream transcription factors, and by its own expression [23] [17]. A wide range of upstream, intronic, and downstream enhancers have been identified that are important in spacio-temporal expression of Pax6 [24] [25] [26] [27] [28] [29] [26] [30].

Mutations of Pax6 lead to eyeless in Drosophila [31], small eye in mouse [32], and aniridia in human [33] [2] [34] [35] [36] [37] [38] [39] [40]. As inferred from Pax6 expression pattern, mutation of PAX6 also disrupt other cellular processes; it is associated with Gillepie syndrome [41] [42], autosomal dominant keratitis[43], Peters anomaly [44], myopia [45], optic nerve malformations [46], and neural developmental anomalies [47] [48] [49] [50] [51].

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FIGURE 1 Pax6 consensus DNA binding sites
A schematic drawing of consensus recognition sequences of PAX6 paired domain and homeodomain.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.