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      Identification of Retinal Transformation Hot Spots in Developing Drosophila Epithelia

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      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          The retinal determination (RD) network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom. Ectopic expression of many members of this network leads to the transformation of non-retinal epithelia into eye tissue. An often-overlooked observation is that only particular cell-populations within a handful of tissues are capable of having their primary developmental instructions superseded and overruled.

          Methodology/Preliminary Findings

          Here we confirm that indeed, only a discrete number of cell populations within the imaginal discs that give rise to the head, antenna, legs, wings and halteres have the cellular plasticity to have their developmental fates altered. In contrast to previous reports, we find that all transformable cell populations do not lie within the TGFβ or Hedgehog signaling domains. Additionally neither signaling cascade alone is sufficient for non-retinal cell types to be converted into retinal tissue. The transformation “hot spots” that we have identified appear to coincide with several previously defined transdetermination “weak spots”, suggesting that ectopic eye formation is less the result of one network overriding the orders of another, as previously thought, but rather is the physical manifestation of redirecting cell populations of enormous cellular plasticity. We also demonstrate that the initiation of eye formation in non-retinal tissues occurs asynchronously compared to that of the normal eye suggesting that retinal development is not under the control of a global developmental clock.

          Conclusions/Significance

          We conclude that the subregions of non-retinal tissues that are capable of supporting eye formation represent specialized cell-populations that have a different level of plasticity than other cells within these tissues and may be the founder cells of each tissue.

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          Most cited references32

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          Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila.

          The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse Small eye (Pax-6) gene and to the Aniridia gene in humans. These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that ey functions in eye morphogenesis. By targeted expression of the ey complementary DNA in various imaginal disc primordia of Drosophila, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that ey is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans, ey may function as a master control gene throughout the metazoa.
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            Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans.

            A Drosophila gene that contains both a paired box and a homeobox and has extensive sequence homology to the mouse Pax-6 (Small eye) gene was isolated and mapped to chromosome IV in a region close to the eyeless locus. Two spontaneous mutations, ey2 and eyR, contain transposable element insertions into the cloned gene and affect gene expression, particularly in the eye primordia. This indicates that the cloned gene encodes ey. The finding that ey of Drosophila, Small eye of the mouse, and human Aniridia are encoded by homologous genes suggests that eye morphogenesis is under similar genetic control in both vertebrates and insects, in spite of the large differences in eye morphology and mode of development.
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              Development of the Drosophila retina, a neurocrystalline lattice.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                7 January 2010
                : 5
                : 1
                : e8510
                Affiliations
                [1]Department of Biology, Indiana University, Bloomington, Indiana, United States of America
                University of Texas MD Anderson Cancer Center, United States of America
                Author notes

                Conceived and designed the experiments: CLS JPK. Performed the experiments: CLS. Analyzed the data: CLS JPK. Wrote the paper: CLS JPK.

                Article
                09-PONE-RA-11201R1
                10.1371/journal.pone.0008510
                2799516
                20062803
                e3752a88-7c38-4744-a28e-1dce6a0ccc5f
                Salzer, Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 23 June 2009
                : 20 November 2009
                Page count
                Pages: 8
                Categories
                Research Article
                Developmental Biology
                Genetics and Genomics
                Cell Biology/Developmental Molecular Mechanisms

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