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      Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects. By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spätzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases.

          Author Summary

          Neurotrophins are secreted proteins that link nervous system structure and function in vertebrates. They regulate neuronal survival, thus adjusting cell populations, and connectivity, enabling the formation of neuronal circuits. They also regulate patterns of dendrites and axons, synaptic function, memory, learning, and cognition; and abnormal neurotrophin function underlies psychiatric disorders. Despite such relevance for nervous system structure and function, neurotrophins have been missing from invertebrates. We show here the identification and functional demonstration of a neurotrophin family in the fruit fly, Drosophila. Our findings imply that the neurotrophins may be present in all animals with a centralised nervous system (motor and sensory systems) or brain, supporting the notion of a common origin for the brain in evolution. This work bridges a void in the understanding of the Drosophila and human nervous systems, and it opens the opportunity to use the powerful fruit fly for neurotrophin related studies.

          Abstract

          Members of the neurotrophin superfamily mediate critical roles in neuronal survival and targeting in the fruit fly Drosophila. Although this is an accepted role for neurotrophins in vertebrates, scant previous evidence has been able to demonstrate such a conserved role in invertebrates.

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          Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization.

          Sea anemones are seemingly primitive animals that, along with corals, jellyfish, and hydras, constitute the oldest eumetazoan phylum, the Cnidaria. Here, we report a comparative analysis of the draft genome of an emerging cnidarian model, the starlet sea anemone Nematostella vectensis. The sea anemone genome is complex, with a gene repertoire, exon-intron structure, and large-scale gene linkage more similar to vertebrates than to flies or nematodes, implying that the genome of the eumetazoan ancestor was similarly complex. Nearly one-fifth of the inferred genes of the ancestor are eumetazoan novelties, which are enriched for animal functions like cell signaling, adhesion, and synaptic transmission. Analysis of diverse pathways suggests that these gene "inventions" along the lineage leading to animals were likely already well integrated with preexisting eukaryotic genes in the eumetazoan progenitor.
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            Evolution and tinkering.

            F Jacob (1977)
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              Comparative genomics of the eukaryotes.

              A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Biol
                pbio
                plbi
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, USA )
                1544-9173
                1545-7885
                November 2008
                18 November 2008
                : 6
                : 11
                : e284
                Affiliations
                [1 ] Neurodevelopment Group, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
                [2 ] Department of Genetics, University of Cambridge, Cambridge, United Kingdom
                [3 ] Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
                [4 ] Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, United Kingdom
                [5 ] National Institute of Biomedical Innovation, Osaka, Japan
                University of Cambridge, United Kingdom
                Author notes
                * To whom correspondence should be addressed. E-mail: a.hidalgo@ 123456bham.ac.uk
                Article
                08-PLBI-RA-0237R7 plbi-06-11-10
                10.1371/journal.pbio.0060284
                2586362
                19018662
                77c12528-5506-42d3-b9fd-f1c6f9bab9c1
                Copyright: © 2008 Zhu et al. 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
                : 21 January 2008
                : 8 October 2008
                Page count
                Pages: 20
                Categories
                Research Article
                Developmental Biology
                Evolutionary Biology
                Genetics and Genomics
                Molecular Biology
                Neuroscience
                Custom metadata
                Zhu B, Pennack JA, McQuilton P, Forero MG, Mizuguchi K, et al. (2008) Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol 6(11): e284. doi: 10.1371/journal.pbio.0060284

                Life sciences
                Life sciences

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