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Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster

Nature Genetics volume 36, pages 31–39 (2004)Cite this article

Abstract

Control of growth determines the size and shape of organs. Localized signals known as 'organizers' and members of the Pax family of proto-oncogenes are both elements in this control. Pax proteins have a conserved DNA-binding paired domain, which is presumed to be essential for their oncogenic activity. We present evidence that the organizing signal Notch does not promote growth in eyes of D. melanogaster through either Eyeless (Ey) or Twin of eyeless (Toy), the two Pax6 transcription factors. Instead, it acts through Eyegone (Eyg), which has a truncated paired domain, consisting of only the C-terminal subregion. In humans and mice, the sole PAX6 gene produces the isoform PAX6(5a) by alternative splicing; like Eyegone, this isoform binds DNA though the C terminus of the paired domain. Overexpression of human PAX6(5a) induces strong overgrowth in vivo, whereas the canonical PAX6 variant hardly effects growth. These results show that growth and eye specification are subject to independent control and explain hyperplasia in a new way.

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Figure 1: Notch signaling is necessary and sufficient to activate eyg expression in the D. melanogaster eye dorsal-ventral organizer.
Figure 2: Eyg lies downstream of and mediates Notch signaling in eye growth.
Figure 3: eyg mRNA expression patterns in wild-type and mutant third-instar discs.
Figure 4: Dose of eyg+ directly affects eye size.
Figure 5: eyg inactivation does not impair eye and head specification.
Figure 6: Boundaries of eyg+ and eyg− cells create new growth-promoting organizers.
Figure 7: Outgrowths or ectopic retinal differentiation responses to human PAX6(5a) or PAX6 in the developing wing.

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Acknowledgements

We thank N. Azpiazu, V. van Heyningen, H. Sun, S. Bray, J. Treisman, A. Baonza, A. Carmena, J. Casal and P. Callaerts for reagents; Bloomington Stock Center for fly stocks; Developmental Studies Hybridoma Bank for antibodies; I. Gutierrez-García, E. Ballesta-Illan and M. Northcote for technical assistance; and P. A. Lawrence, M. Freeman, D. Page, L. A. Garcia-Alonso, M. Millan, F. Casares and F. Viana for critical reading of the manuscript. Part of this work was done in the laboratory of P. A. Lawrence at the Medical Research Council Laboratory of Molecular Biology in Cambridge (UK). This work was supported by grants from Fondo de Investigaciones Sanitarias and Ministerio de Ciencia y Tecnología from Spain and by a European Molecular Biology Organisation Young Investigator Award to M.D.

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  1. Monica Beneyto

    Present address: Mental Health Research Institute, Department of Psychiatry, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, Michigan, 48109, USA

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  1. Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Miguel Hernández, Campus de San Juan, Apartado 18, Sant Joan d'Alacant, E-03550, Spain

    Maria Dominguez, Dolors Ferres-Marco, Francisco J Gutierrez-Aviño, Stephan A Speicher & Monica Beneyto

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Correspondence to Maria Dominguez.

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Dominguez, M., Ferres-Marco, D., Gutierrez-Aviño, F. et al. Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat Genet 36, 31–39 (2004). https://doi.org/10.1038/ng1281

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