Pax Genes: Evolution and Function

Abstract

The transcription factors of the Pax protein family have been conserved throughout metazoan evolution and play essential roles in brain development and organogenesis. Loss‐of‐function and gain‐of‐function mutations in PAX genes cause inherited disease syndromes and tumor formation respectively.

Keywords: Pax; transcription factor; paired domain; gene duplications; brain development; organogenesis; haploinsufficiency; inherited disease; tumorigenesis

Figure 1.

Structure and classification of mammalian Pax proteins. The different domains of Pax proteins are indicated. The consensus sequence of the conserved octapeptide (OP) is (Y/H)SI(N/D/S)GILG. PD: paired domain; HD: homeodomain; TAD: transactivation domain; PST: proline–serine–threonine.

Figure 2.

Structure and evolution of the paired domain. (a) Sequence conservation of the paired domain, the structure of which indicates the positions of α helices and β sheets. The paired domain sequences are shown without the additional amino acids that can be inserted by alternative splicing to modify the DNA‐binding function of Pax proteins. GenBank protein accession numbers: human (hu) Pax1 (P15863), Pax2 (Q02962), Pax3 (14250714), Pax4 (O43316), Pax5 (Q02548), Pax6 (383296), Pax7 (P23759), Pax8 (Q06710), Pax9 (AAH01159); amphioxus (am) Branchiostoma floridae Pax19 (644847), Pax258 (3025752), Pax37 (9621907), Pax46 (3204114); cnidarian (cn) Acropora millepora PaxA (AAC15713), PaxB (AAF64460), PaxC (AAC15711), PaxD (AAF64461), and Caenorhabditis elegans (ce) Tc1 transposase (17510681). The cephalochordate amphioxus is considered to be at the phylogenetic base of vertebrates. (b) Phylogenetic tree based on the sequence alignment shown in (a). (c) The consensus recognition sequence of the Pax6 paired domain is shown together with the three‐dimensional structure of the Pax6 paired domain–DNA complex (Xu et al., ).

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References

Barr FG (2001) Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma. Oncogene 20: 5736–5746.

Bopp D, Burri M, Baumgartner S, Frigerio G and Noll M (1986) Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell 47: 1033–1040.

Bouchard M, Pfeffer P and Busslinger M (2000) Functional equivalence of the transcription factors Pax2 and Pax5 in mouse development. Development 127: 3703–3713.

Bouchard M, Souabni A, Mandler M, Neubüser A and Busslinger M (2002) Nephric lineage specification by Pax2 and Pax8. Genes and Development 16: 2958–2970.

Chi N and Epstein JA (2002) Getting your Pax straight: Pax proteins in development and disease. Trends in Genetics 18: 41–47.

Czerny T, Schaffner G and Busslinger M (1993) DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes and Development 7: 2048–2061.

Halder G, Callaerts P and Gehring W (1995) Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267: 1788–1792.

Hill RE, Favor J, Hogan BL et al. (1991) Mouse small eye results from mutations in a paired‐like homeobox‐containing gene. Nature 354: 522–525.

Miller DJ, Hayward DC, Reece‐Hoyes JS et al. (2000) PAXgene diversity in the basal cnidarian Acropora millepora (Cnidaria, Anthozoa): implications for the evolution of the PAX gene family. Proceedings of the National Academy of Sciences of the USA 97: 4475–4480.

Nutt SL, Heavey B, Rolink AG and Busslinger M (1999) Commitment to the B‐lymphoid lineage depends on the transcription factor Pax5. Nature 401: 556–562.

St‐Onge L, Sosa‐Pineda B, Chowdhury K, Mansouri A and Gruss P (1997) Pax6 is required for differentiation of glucagon‐producing α‐cells in mouse pancreas. Nature 387: 406–409.

Stoykova A, Fritsch R, Walther C and Gruss P (1996) Forebrain patterning defects in Small eye mutant mice. Development 122: 3453–3465.

Xu HE, Rould MA, Xu W et al. (1999) Crystal structure of the human Pax6 paired domain–DNA complex reveals specific roles for the linker region and carboxy‐terminal subdomain in DNA binding. Genes and Development 13: 1263–1275.

Ye W, Bouchard M, Stone D et al. (2001) Distinct regulators control the induction, positioning and maintenance of the mid‐hindbrain organizer signal FGF8. Nature Neuroscience 4: 1175–1181.

Further Reading

Chow RL, Altmann CR, Lang RA and Hemmati‐Brivanlou A (1999) Pax6 induces ectopic eyes in a vertebrate. Development 126: 4213–4222.

Eberhard D, Jiménez G, Heavey B and Busslinger M (2000) Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family. EMBO Journal 19: 2292–2303.

Ericson J, Rashbass P, Schedl AB et al. (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90: 169–180.

Gehring WJ and Ikeo K (1999) Pax6: mastering eye morphogenesis and eye evolution. Trends in Genetics 15: 371–377.

Kozmik Z (2005) Pax genes in eye development and evolution. Current Opinion in Genetics and Development 15: 430–438.

Kroll TG, Sarraf P, Pecciarini L et al. (2000) PAX8‐PPARγ1 fusion oncogen in human thyroid carcinoma. Science 289: 1357–1360.

Mansouri A, Chowdhury K and Gruss P (1998) Follicular cells of the thyroid gland require Pax8 gene function. Nature Genetics 19: 87–90.

Mansouri A, Hallonet M and Gruss P (1996) PAX genes and their roles in cell differentiation and development. Current Opinion in Cell Biology 8: 851–857.

Peters H, Neubüser A, Kratochwil K and Balling R (1998) Pax9‐deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes and Development 12: 2735–2747.

Seale P, Sabourin LA, Girgis‐Gabardo A et al. (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102: 777–786.

Tajbakhsh S, Rocancourt D, Cossu G and Buckingham M (1997) Redefining the genetic hierarchies controlling skeletal myogenesis: Pax‐3 and Myf‐5 act upstream of MyoD. Cell 89: 127–138.

Web Links

forkhead box O1A (rhabdomyosarcoma)(FOXO1A); LocusID: 2308. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2308

forkhead box O1A (rhabdomyosarcoma)(FOXO1A); MIM number: 136533. OMIM: http://www3.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?136533

paired box gene 6 (aniridia, keratitis)(PAX6); LocusID: 5080. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5080

paired box gene 6 (aniridia, keratitis)(PAX6); MIM number: 106210. OMIM: http://www3.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?106210

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How to Cite close
Bouchard, Maxime, Schleiffer, Alexander, Eisenhaber, Frank, and Busslinger, Meinrad(Apr 2008) Pax Genes: Evolution and Function. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005114.pub2]