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Paired box protein Pax-6 (Gene PAX6) Homo sapiensPax family genes characterized by the presence of a highly conserved DNA-binding motif (paired domain) regulate embryonic pattern formation and cell proliferation and differentiation during embryonic organogenesis. The Pax subfamily group 4 composed of Pax4 and Pax6 contains a homeodomain in addition to the paired box domain common to the family, Dahl E, et al. (1997). The PAX6 (map locus: 11p13) gene product, paired box gene 6/Pax6, exists in several isoforms. Pax6-1 and Pax6,5a are the most extensively studied isoforms. Pax6-1 (Pax6-a) is a 422 AA (46.6 kDa) protein that contains a paired box (paired domain), 127 AA (4 to 130); a DNA-binding homeobox (homeodomain) 60 AA (210 to 269), a Gln/Gly-rich region, 79 AA (131 to 209) and a proline/serine/threonine (P/S/T)-rich C-terminal domain. Pax6,5a, 436 AA, is altered by a 5a insertion (5a exon) within the paired box region; wherein, Gln47 is replaced with a 15 AA sequence. Different aspects of Pax6 gene function are mediated by different isoforms of the Pax6 protein. The distinct roles in brain development of the paired domain, homeodomain and 5a splice have been reviewed, Haubst N et al. (2004). The 5a positive isoform has recently been linked to development of the fovea within the vertebrate retina, Azuma N, et al. (2005). Pax-6 is widely expressed in the developing CNS during the neural plate stage. It is expressed in the neural tube just after its closure and subsequently it is spatially and temporally restricted within the telencephalon and diencephalon of the forebrain, Mastick, GS, et al. (1997); the optic and nasal placodes, Li HS, et al. (1994); the rhombencephalon (hindbrain); the somites and the spinal cord, Gerard M, et al. (1995), Amirthalingam K, et al. (1995). Pax6 is found in both layers of the optic cup, the optic stalk and prospective corneal epithelium; in the infundibulum and in Rathke’s pouch, Terzic J and Saraga-Babic M. (1999). In developing human brain, Pax6 is strongly expressed in proliferating radial glia (RG) cells and some neuronal and intermediate progenitors within the dorsal and ventral proliferative zones, Mo Z and Zecevic N. (2008). It is required for development of radial glial and cortical cells and neuronal migration, Warren N, et al. (1999). Pax6 contributes to both embryonic and adult neurogenesis as a multifunctional regulator, Osumi N, et al. (2008). Pax6 is a patterning and arealization dorsalizing factor that regulates dorso-ventral and anterior-posterior neural cell specification, migration and axonal projections within the forebrain telencephalon, Stoykova A, et al. (2000) and the diencephalon (thalamocortical development), Kawano H, et al. (1999), Pratt T, et al. (2000; the hindbrain (rhombencephalon), Engelkamp D, et al. (1999); Osumi N, et al. (1997) and the spinal cord, Sapir T, et al. (2004). Pax6 is required to establish the diencephalic/mesencephalic (forebrain/midbrain) boundary, Matsunaga E, at al. (2000). Pax6 supports the regionalization of the telencephalon by limiting the invasion of the cortex by cells originating in the ganglionic eminence, Chapouton P, et al. (1999). Pax6 is critical to the formation of the first two major longitudinal tracts, the tract of the postoptic commissure (TPOC) (a major pathway for forebrain dopaminergic projections) and the stria medullaris, in embryonic mouse forebrain, Nural HF and Mastick GS (2004). Pax-6 is required for thalamocortical pathway formation in fetal rats, Kawano H, et al. (1999). Pax6 is required for the formation of the subcommissural organ (SCO) via development of the diencephalic dorsal midline secretory radial glia, Estivill-Torrús G, et al. (2001). Pax6 is a master control gene for eye development, Gehring WJ, (1996) that is required for the proper formation of the lens, iris, retina and cornea, Davis J. et al. (2003); Baumer N, et al. (2002). Mutations in Pax6 are linked to Aniridia and small eye. Pax6 is a competence factor that supports FGF10 induction of lacrimal gland development, Makarenkova HP, et al. (2000). Pax6 is present in all cells that form the neural retina and pigment epithelium including the lens, cornea and the neural and pigmented retinas, Macdonald R, et al. (1995), Davis JA and Reed RR, (1996). Pax6 is also expressed in surface epithelia of adult cornea and conjunctiva, Koroma BM, et al. (1997). The relative abundance of Pax6-5a isoform varies between lens and iris of the mature bovine eye, Jaworski C, et al. (1997). Pax-6 is required for the formation of the pineal gland, Mitchell TN, et al. (2003) and it is dorsalizing factor within the developing pituitary, Kioussi C, et al. (1999). Pax-6 is expressed in ectoderm derived tissues outside the nervous system. It is required for the differentiation of glucagon-producing alpha-cells within the pancreas, St-Onge, et al. (1997) and differentiation of gastrointestinal endocrine cells, Larsson LI, et al. (1998). Pax6 is expressed in the majority of pancreatic adenocarcinomas, Lang D, et al. (2008) and in glioblastoma multiforme (GBM), an invasive brain cancer, Zhou YH, et al. (2005). In GBM, Pax6 is reported to be a repressor of invasiveness, Mayes DA, et al. (2006). There are over 1300 Pax6 citations in Pubmed. Sigma offers antibodies and shRNAs useful for the study of PAX6 gene products. References: Amirthalingam K, et al. (1995) Embryonic expression and DNA-binding properties of zebrafish pax-6. Biochem Biophys Res Commun. 215: 122-128. |
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