PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional suppression by the tumor suppressor gene WT1. Pax 2 is a transcription factor controlled by the signaling molecules Wnt1 and Fgf8. Pax2 along with other transcription factors Pax5, Pax8, En1, and En 2 are expressed across the Otx2-Gbx2 boundary in the mid-hindbrain region. These transcription factors work with the signaling molecules Wnt1 and Fgf8 to maintain the MHB organizer. The MHB controls midbrain and cerebellum development. Pax2 is the earliest known gene to be expressed across the Otx2-Gbx2 boundary. It is first expressed in the late primitive streak stage and is expressed in a narrow ring centered at the MHB during somitogenesis. Transgene expression of the mid-hindbrain and developing kidney is directed by Pax2. There are three distinct MHB-specific enhancers in the upstream region of Pax2. Expression at the MHB from the four-somite stage onwards is directed by the two late enhancers in the proximal and distal regions of Pax2. The early enhancer located in the intermediate region activates the mid-hindbrain region of late gastrula embryos. The activation of Pax2, Pax5, and Pax8 is a conserved feature of all vertebrates.
Mutations within PAX2 have been shown to result in optic nerve colobomas and renalhypoplasia. Alternative splicing of this gene results in multiple transcript variants. Pax2 and Pax8 are also necessary for the formation of the pronephros and subsequent kidney structures. Pax2 and Pax8 regulate the expression of Gata3. Without these genes mutations in the urogenital system arise.
^Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes". Mamm. Genome4 (2): 78–82. doi:10.1007/BF00290430. PMID8431641.
^Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (April 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9". Nat. Genet.3 (4): 292–8. doi:10.1038/ng0493-292. PMID7981748.
^Pfeffer, Peter L.; Bernhard Payter; Gerlinde Reim; Marina Pasca di Magliano; Meinrad Busslinger (2001). "The activation and maintenance of Pax2 expression at the mid-hindbrain boundary is controlled by separate enhancers". Development (133): 307–318.
^Grote, David; Souabni, Abdallah, Busslinger, Meinrad, Bouchard, Maxime. "Pax2/8-regulated Gata3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney". Devopment (133): 53–61.Cite uses deprecated parameter |coauthors= (help)
Eccles MR, He S, Legge M et al. (2003). "PAX genes in development and disease: the role of PAX2 in urogenital tract development.". Int. J. Dev. Biol.46 (4): 535–44. PMID12141441.CS1 maint: Explicit use of et al. (link)
Eccles MR, Wallis LJ, Fidler AE et al. (1992). "Expression of the PAX2 gene in human fetal kidney and Wilms' tumor.". Cell Growth Differ.3 (5): 279–89. PMID1378753.CS1 maint: Explicit use of et al. (link)
Sanyanusin P, Schimmenti LA, McNoe LA et al. (1995). "Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux.". Nat. Genet.9 (4): 358–64. doi:10.1038/ng0495-358. PMID7795640.CS1 maint: Explicit use of et al. (link)
Ward TA, Nebel A, Reeve AE, Eccles MR (1995). "Alternative messenger RNA forms and open reading frames within an additional conserved region of the human PAX-2 gene.". Cell Growth Differ.5 (9): 1015–21. PMID7819127.
Stapleton P, Weith A, Urbánek P et al. (1995). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9.". Nat. Genet.3 (4): 292–8. doi:10.1038/ng0493-292. PMID7981748.CS1 maint: Explicit use of et al. (link)
Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes.". Mamm. Genome4 (2): 78–82. doi:10.1007/BF00290430. PMID8431641.
Sanyanusin P, McNoe LA, Sullivan MJ et al. (1996). "Mutation of PAX2 in two siblings with renal-coloboma syndrome.". Hum. Mol. Genet.4 (11): 2183–4. doi:10.1093/hmg/4.11.2183. PMID8589702.CS1 maint: Explicit use of et al. (link)
Dehbi M, Ghahremani M, Lechner M et al. (1996). "The paired-box transcription factor, PAX2, positively modulates expression of the Wilms' tumor suppressor gene (WT1).". Oncogene13 (3): 447–53. PMID8760285.CS1 maint: Explicit use of et al. (link)
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res.6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Tavassoli K, Rüger W, Horst J (1998). "Alternative splicing in PAX2 generates a new reading frame and an extended conserved coding region at the carboxy terminus.". Hum. Genet.101 (3): 371–5. doi:10.1007/s004390050644. PMID9439670.
Devriendt K, Matthijs G, Van Damme B et al. (1998). "Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330).". Hum. Genet.103 (2): 149–53. doi:10.1007/s004390050798. PMID9760197.CS1 maint: Explicit use of et al. (link)