Mutational analysis of the eyeless gene and phenotypic rescue reveal that an intact Eyeless protein is necessary for normal eye and brain development in Drosophila

Developmental Biology

Volumn 334, Issue 2, 2009, Pages 503-512

  Clements, Jason ^a,b   Hens, Korneel ^a   Merugu, Srinivas ^b   Dichtl, Beatriz ^b   de Couet, H Gert ^c   Callaerts, Patrick ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b University of Houston   (United States)

^c UNIVERSITY OF HAWAII   (United States)

Author keywords

Drosophila; Eyeless; Homeodomain; Paired domain; Pax6; Transcription factor

Indexed keywords

EYELESS PROTEIN; TRANSCRIPTION FACTOR GAL4; TRANSCRIPTION FACTOR PAX6; UNCLASSIFIED DRUG;

ALLELE; ANIMAL TISSUE; ARTICLE; BRAIN DEVELOPMENT; CONTROLLED STUDY; DROSOPHILA; EYE DEVELOPMENT; IN VIVO STUDY; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION;

EID: 70349296747     PISSN: 00121606     EISSN: 1095564X     Source Type: Journal    
DOI: 10.1016/j.ydbio.2009.08.003     Document Type: Article

References (76)

1. Adachi Y., Hauck B., Clements J., Kawauchi H., Kurusu M., Totani Y., Kang Y.Y., Eggert T., Walldorf U., Furukubo-Tokunaga K., et al. Conserved cis-regulatory modules mediate complex neural expression patterns of the eyeless gene in the Drosophila brain. Mech. Dev. 120 (2003) 1113-1126
2. Azuma N., Hotta Y., Tanaka H., and Yamada M. Missense mutations in the PAX6 gene in Aniridia. Invest. Ophthalmol. Vis. Sci. 39 (1998) 2524-2528
3. Azuma N., Yamaguchi Y., Handa H., Tadokoro K., Asaka A., Kawase E., and Yamada M. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am. J. Hum. Genet. 72 (2003) 1565-1570
4. Benassayag C., Plaza S., Callaerts P., Clements J., Romeo Y., Gehring W.J., and Cribbs D.L. Evidence for a direct functional antagonism of the selector genes proboscipedia and eyeless in Drosophila head development. Development 130 (2003) 575-586
5. Billeter M., Qian Y.Q., Otting G., Müller M., Gehring W., and Wüthrich K. Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex. J. Mol. Biol. 234 (1993) 1084-1097
6. Bopp D., Burri M., Baumgartner S., Frigerio G., and Noll M. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell 47 (1986) 1033-1040
7. Brand A.H., and Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118 (1993) 401-415
8. Buszczak M., Paterno S., Lighthouse D., Bachman J., Planck J., Owen S., Skora A.D., Nystul T.G., Ohlstein B., Allen A., et al. The Carnegie Protein Trap Library: a versatile tool for Drosophila developmental studies. Genetics 175 (2007) 1505-1531
9. Callaerts P., Halder G., and Gehring W.J. PAX-6 in development and evolution. Annu. Rev. Neurosci. 20 (1997) 483-532
10. Callaerts P., Leng S., Clements J., Benassayag C., Cribbs D., Kang Y.Y., Walldorf U., Fischbach K.F., and Strauss R. Drosophila Pax-6/eyeless is essential for normal adult brain structure and function. J. Neurobiol. 46 (2001) 73-88
11. Callaerts P., Clements J., Francis C., and Hens K. Pax6 and eye development in Arthropoda. Arthropod. Struct. Dev. 35 (2006) 379-391
12. Carrière C., Plaza S., Caboche J., Dozier C., Bailly M., Martin P., and Saule S. Nuclear localization signals, DNA binding, and transactivation properties of quail Pax-6 (Pax-QNR) isoforms. Cell Growth Differ. 6 (1995) 1531-1540
13. Chow R.L., Altmann C.R., Lang R.A., and Hemmati-Brivanlou A. Pax6 induces ectopic eyes in a vertebrate. Development 126 (1999) 4213-4222
14. Clements J., Hens K., Francis C., Schellens A., and Callaerts P. Conserved role for the Drosophila Pax6 homolog Eyeless in differentiation and function of insulin-producing neurons. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 16183-16188
15. s signaling in Drosophila mushroom bodies. Science 274 (1996) 2104-2107
16. Czerny T., and Busslinger M. DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol. Cell. Biol. 15 (1995) 2858-2871
17. Epstein J.A., Glaser T., Cai J., Jepeal L., Walton D.S., and Maas R.L. Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. Genes Dev. 8 (1994) 2022-2034
18. 10Neu: An extension of the Pax6 allelic series and the identification of two possible hypomorph alleles in the mouse Mus musculus. Genetics 159 (2001) 1689-1700
19. Fitzsimmons D., Hodsdon W., Wheat W., Maira S.-M., Wasylyk B., and Hagman J. Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter. Genes Dev. 10 (1996) 2198-2211
20. Fortin A.S., Underhill D.A., and Gros P. Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain. Hum. Mol. Genet. 6 (1997) 1781-1790
21. Fortin A.S., Underhill D.A., and Gros P. Helix 2 of the paired domain plays a key role in the regulation of DNA-binding by the Pax-3 homeodomain. Nucleic Acids Res. 26 (1998) 4574-4581
22. Frigerio G., Burri M., Bopp D., Baumgartner S., and Noll M. Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell 47 (1986) 735-746
23. Gehring W.J., and Ikeo K. Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet. 15 (1999) 371-377
24. Glaser T., Jepeal L., Edwards J.G., Young S.R., Favor J., and Maas R.L. PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat. Genet. 7 (1994) 463-471
25. Glaser T., Walton D.S., Cai J., Epstein J.A., Jepeal L., and Maas R.L. PAX6 gene mutations in aniridia. In: Wiggs J.L. (Ed). Molecular Genetics of Ocular Disease (1995), Wiley-Liss, Inc., New York 51-82
26. Grindley J.C., Davidson D.R., and Hill R.E. The role of Pax-6 in eye and nasal development. Development 121 (1995) 1433-1442
27. Halder G., Callaerts P., and Gehring W.J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267 (1995) 1788-1792
28. Halder G., Callaerts P., Flister S., Walldorf U., Kloter U., and Gehring W.J. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125 (1998) 2181-2191
29. Hanson I.M., Seawright A., Hardman K., Hodgson S., Zaletayev D., Fekete G., and van Heyningen V. PAX6 mutations in aniridia. Hum. Mol. Genet. 2 (1993) 915-920
30. Hill R.E., Favor J., Hogan B.L., Ton C.C., Saunders G.F., Hanson I.M., Prosser J., Jordan T., Hastie N.D., and van Heyningen V. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354 (1991) 522-525
31. Jun S., and Desplan C. Cooperative interactions between paired domain and homeodomain. Development 122 (1996) 2639-2650
32. Kammermeier L., Leemans R., Hirth F., Flister S., Wenger U., Walldorf U., Gehring W.J., and Reichert H. Differential expression and function of the Drosophila Pax6 genes eyeless and twin of eyeless in embryonic central nervous system development. Mech. Dev. 103 (2001) 71-78
33. Kozmik Z. The role of Pax genes in eye evolution. Brain Res. Bull. 75 (2008) 335-339
34. Kozmik Z., Czerny T., and Busslinger M. Alternatively spliced insertions in the paired domain restrict the DNA sequence specificity of Pax6 and Pax8. EMBO J. 16 (1997) 6793-6803
35. Kurusu M., Nagao T., Walldorf U., Flister S., Gehring W.J., and Furukubo-Tokunaga K. Genetic control of development of the mushroom bodies, the associative learning centers in the Drosophila brain, by the eyeless, twin of eyeless, and dachshund genes. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 2140-2144
36. Laughon A., and Scott M.P. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature 310 (1984) 25-31
37. Lewis E.B., and Bacher F. Method of feeding ethyl methane sulphonate (EMS) to Drosophila males. Dros. Inf. Serv. 43 (1968) 193-194
38. Lindsley D., and Zimm G. The Genome of Drosophila melanogaster (1992), Academic Press, New York
39. Marquardt T., Ashery-Padan R., Andrejewski N., Scardigli R., Guillemot F., and Gruss P. Pax6 is required for the multipotent state of retinal progenitor cells. Cell 105 (2001) 43-55
40. Mastick G.S., and Andrews G.L. Pax6 regulates the identity of embryonic diencephalic neurons. Mol. Cell. Neurosci. 17 (2001) 190-207
41. Mastick G.S., Davis N.M., Andrews G.L., and Easter Jr. S.S. Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain. Development 124 (1997) 1985-1997
42. Matsunaga E., Araki I., and Nakamura H. Pax6 defines the di-mesencephalic boundary by repressing En1 and Pax2. Development 127 (2000) 2357-2365
43. Morrison D., FitzPatrick D., Hanson I., Williamson K., van Heyningen V., Fleck B., Jones I., Chalmers J., and Campbell H. National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology. J. Med. Genet. 39 (2002) 16-22
44. Noveen A., Daniel A., and Hartenstein V. Early development of the Drosophila mushroom body: the roles of eyeless and dachshund. Development 127 (2000) 3475-3488
45. Osumi N., Hirota A., Ohuchi H., Nakafuku M., Iimura T., Kuratani S., Fujiwara M., Noji S., and Eto K. Pax-6 is involved in the specification of hindbrain motor neuron subtype. Development 124 (1997) 2961-2972
46. Punzo C., Kurata S., and Gehring W.J. The eyeless homeodomain is dispensable for eye development in Drosophila. Genes Dev. 15 (2001) 1716-1723
47. Quinn J.C., West J.D., and Hill R.E. Multiple functions for Pax6 in mouse eye and nasal development. Genes Dev. 10 (1996) 435-446
48. Quiring R., Walldorf U., Kloter U., and Gehring W.J. Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265 (1994) 785-789
49. Redeker E.J.W., de Visser A.S.H., Bergen A.A.B., and Mannens M.M.A.M. Multiplex ligation-dependant probe amplification (MLPA) enhances the molecular diagnosis of aniridia and related disorders. Mol. Vis. 14 (2008) 836-840
50. Scott M.P., Tamkun J.W., and Hartzell G.W. The structure and function of the homeodomain. Biochim. Biophys. Acta 989 (1989) 25-48
51. Sheng G., Harris E., Bertuccioli C., and Desplan C. Modular organization of Pax/Homeodomain proteins in transcriptional regulation. Biol. Chem. 378 (1997) 863-872
52. Singh S., Stellrecht C.M., Tang H.K., and Saunders G.F. Modulation of PAX6 homeodomain function by the paired domain. J. Biol. Chem. 275 (2000) 17306-17313
53. Singh S., Chao L.Y., Mishra R., Davies J., and Saunders G.F. Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Hum. Mol. Genet. 10 (2001) 911-918
54. Stoykova A., Treichel D., Hallonet M., and Gruss P. Pax6 modulates the dorsoventral patterning of the mammalian telencephalon. J. Neurosci. 20 (2000) 8042-8050
55. In: Sullivan W., Ashburner M., and Hawley R.S. (Eds). Drosophila protocols (2000), Cold Spring Harbor Laboratory Press, Cold Spring Harbor
56. Takahashi M., and Osumi N. Pax6 regulates specification of ventral neurone subtypes in the hindbrain by establishing progenitor domains. Development 129 (2002) 1327-1338
57. Tang H.K., Singh S., and Saunders G.F. Dissection of the transactivation function of the transcription factor encoded by the eye developmental gene PAX6. J. Biol. Chem. 273 (1998) 7210-7221
58. Thaung C., West K., Clark B.J., McKie L., Morgan J.E., Arnold K., Nolan P.M., Peters J., Hunter A.J., Brown S.D.M., et al. Novel ENU-induced eye mutations in the mouse: models for human eye disease. Hum. Mol. Genet. 11 (2002) 755-767
59. Ton C.C.T., Hirvonen H., Miwa H., Weil M.M., Monaghan P., Jordan T., van Heyningen V., Hastie N.D., Meijers-Heijboer H., Drechsler M., et al. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 67 (1991) 1059-1074
60. Treisman J., Gönczy P., Vashishtha M., Harris E., and Desplan C. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell 59 (1989) 553-562
61. Treisman J., Harris E., and Desplan C. The paired box encodes a second DNA-binding domain in the paired homeodomain protein. Genes Dev. 5 (1991) 594-604
62. Treisman J., Harris E., Wilson D., and Desplan C. The homeodomain: a new face for the helix-turn-helix?. BioEssays 14 (1992) 145-150
63. Underhill D.A., and Gros P. The paired-domain regulates DNA binding by the homeodomain within the intact Pax-3 protein. J. Biol. Chem. 272 (1997) 14175-14182
64. Underhill D.A., Vogan K.J., and Gros P. Analysis of the mouse Splotch-delayed mutation indicates that the Pax-3 paired domain can influence homeodomain DNA-binding activity. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 3692-3696
65. van Heyningen V., and Williamson K.A. PAX6 in sensory development. Hum. Mol. Genet. 11 (2002) 1161-1167
66. Vogan K.J., and Gros P. The C-terminal subdomain makes an important contribution to the DNA binding activity of the Pax-3 paired domain. J. Biol. Chem. 272 (1997) 28289-28295
67. Vogan K.J., Underhill D.A., and Gros P. An alternative splicing event in the Pax-3 paired domain identifies the linker region as a key determinant of paired domain DNA-binding activity. Mol. Cell. Biol. 16 (1996) 6677-6686
68. Walther C., and Gruss P. Pax-6, a murine paired box gene, is expressed in the developing CNS. Development 113 (1991) 1435-1449
69. Walther C., Guenet J.-L., Simon D., Deutsch U., Jostes B., Goulding M.D., Plachov D., Balling R., and Gruss P. Pax: a murine multigene family of paired box-containing genes. Genomics 11 (1991) 424-434
70. Warren N., and Price D.J. Roles of Pax-6 in murine diencephalic development. Development 124 (1997) 1573-1582
71. Wawersik S., and Maas R.L. Vertebrate eye development as modeled in Drosophila. Hum. Mol. Genet. 9 (2000) 917-925
72. Wilson D., Sheng G., Lecuit T., Dostatni N., and Desplan C. Cooperative dimerization of paired class homeodomains on DNA. Genes Dev. 7 (1993) 2120-2134
73. Wilson D.S., Guenther B., Desplan C., and Kuriyan J. High resolution crystal structure of a paired (Pax) class cooperative homeodomain dimer on DNA. Cell 82 (1995) 709-719
74. Wisniewski J., Orosz A., Allada R., and Wu C. The C-terminal region of Drosophila heat shock factor (HSF) contains a constitutively functional transactivation domain. Nucl. Acids Res. 24 (1996) 367-374
75. Xu H.E., Rould M.A., Xu W., Epstein J.A., Maas R.L., and Pabo C.O. 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 Dev. 13 (1999) 1263-1275
76. Xu W., Rould M.A., Jun S., Desplan C., and Pabo C.O. Crystal structure of a paired domain-DNA complex at 2.5 Å resolution reveals structural basis for Pax developmental mutations. Cell 80 (1995) 639-650