The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates.

The fly eyes absent (eya) gene which is essential for compound eye development in Drosophila, was shown to be functionally replaceable in eye development by a vertebrate Eya homolog. The relationship between eya and that of the eyeless gene, a Pax-6 homolog, critical for eye formation in both flies and man, was defined: eya was found to be essential for eye formation by eyeless. Moreover, eya could itself direct ectopic eye formation, indicating that eya has the capacity to function as a master control gene for eye formation. Finally, we show that eya and eyeless together were more effective in eye formation than either gene alone. These data indicate conservation of the pathway of eya function between flies and vertebrates; they suggest a model whereby eya/Eya gene function is essential for eye formation by eyeless/Pax-6, and that eya/Eya can in turn mediate, via a regulatory loop, the activity of eyeless/Pax-6 in eye formation.

[1]  G. Saunders,et al.  Mouse Small eye results from mutations in a paired-like homeobox-containing gene , 1991, Nature.

[2]  N. Bonini,et al.  Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm. , 1997, Development.

[3]  R. Maas,et al.  Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene , 1992, Nature Genetics.

[4]  Seymour Benzer,et al.  The eyes absent gene: Genetic control of cell survival and differentiation in the developing Drosophila eye , 1993, Cell.

[5]  P. Callaerts,et al.  Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata. , 1997, Development.

[6]  M. Lyon,et al.  Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. , 1986, Journal of embryology and experimental morphology.

[7]  L. Strong,et al.  Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region , 1991, Cell.

[8]  N. Spinner,et al.  Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. , 1997, Genome research.

[9]  I. Hanson,et al.  Pax6: more than meets the eye. , 1995, Trends in genetics : TIG.

[10]  C. Zuker.  On the evolution of eyes: would you like it simple or compound? , 1994, Science.

[11]  M. C. Ellis,et al.  Expression of Drosophila glass protein and evidence for negative regulation of its activity in non-neuronal cells by another DNA-binding protein. , 1993, Development.

[12]  S. Benzer,et al.  Transvection at the eyes absent gene of Drosophila. , 1994, Genetics.

[13]  P. Callaerts,et al.  New perspectives on eye evolution. , 1995, Current opinion in genetics & development.

[14]  J. O'Tousa,et al.  sine oculis is a homeobox gene required for Drosophila visual system development. , 1994, Genetics.

[15]  W. Gehring,et al.  Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. , 1994, Science.

[16]  V. Hartenstein,et al.  The drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system , 1994, Neuron.

[17]  G. Rubin,et al.  Genetic transformation of Drosophila with transposable element vectors. , 1982, Science.

[18]  G. Mardon,et al.  Ectopic eye development in Drosophila induced by directed dachshund expression. , 1997, Development.

[19]  J. Weissenbach,et al.  A human homologue of the Drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene family , 1997, Nature Genetics.

[20]  A. Brand,et al.  Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[21]  S. Zipursky,et al.  Early pattern formation in the developing Drosophila eye. , 1994, Trends in cell biology.

[22]  N. Copeland,et al.  Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. , 1995, Development.

[23]  P. Callaerts,et al.  Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. , 1995, Science.

[24]  U. Heberlein,et al.  Mechanisms of drosophila retinal morphogenesis: The virtues of being progressive , 1995, Cell.

[25]  W. Gelbart,et al.  An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila. , 1991, Development.

[26]  E. Wieschaus,et al.  Mutations affecting the pattern of the larval cuticle in drosophila melanogaster 3. zygotic loci on the x chromosome and 4th chromosome , 1984 .

[27]  S. Hodgson,et al.  The human PAX6 gene is mutated in two patients with aniridia , 1992, Nature Genetics.

[28]  R. Maas,et al.  Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode. , 1997, Development.

[29]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.