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      Orthodenticle is necessary for survival of a cluster of clonally related dopaminergic neurons in the Drosophila larval and adult brain

      research-article
      1 , 2 , , 1 , 3 , 1 ,
      Neural Development
      BioMed Central

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          Abstract

          Background

          The dopaminergic (DA) neurons present in the central brain of the Drosophila larva are spatially arranged in stereotyped groups that define clusters of bilaterally symmetrical neurons. These clusters have been classified according to anatomical criteria (position of the cell bodies within the cortex and/or projection pattern of the axonal tracts). However, information pertaining to the developmental biology, such as lineage relationship of clustered DA neurons and differential cell subtype-specific molecular markers and mechanisms of differentiation and/or survival, is currently not available.

          Results

          Using MARCM and twin-spot MARCM techniques together with anti-tyrosine hydroxylase immunoreactivity, we have analyzed the larval central brain DA neurons from a developmental point of view and determined their time of birth, their maturation into a DA neurotransmitter phenotype as well as their lineage relationships. In addition, we have found that the homeodomain containing transcription factor Orthodenticle (Otd) is present in a cluster of clonally related DA neurons in both the larval and adult brain. Taking advantage of the otd hypomorphic mutation ocelliless ( oc) and the oc2-Gal4 reporter line, we have studied the involvement of orthodenticle ( otd) in the survival and/or cell fate specification of these post-mitotic neurons.

          Conclusions

          Our findings provide evidence of the presence of seven neuroblast lineages responsible for the generation of the larval central brain DA neurons during embryogenesis. otd is expressed in a defined group of clonally related DA neurons from first instar larvae to adulthood, making it possible to establish an identity relationship between the larval DL2a and the adult PPL2 DA clusters. This poses otd as a lineage-specific and differential marker of a subset of clonally related DA neurons. Finally, we show that otd is required in those DA neurons for their survival.

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          Most cited references30

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          Mechanisms of asymmetric stem cell division.

          Stem cells self-renew but also give rise to daughter cells that are committed to lineage-specific differentiation. To achieve this remarkable task, they can undergo an intrinsically asymmetric cell division whereby they segregate cell fate determinants into only one of the two daughter cells. Alternatively, they can orient their division plane so that only one of the two daughter cells maintains contact with the niche and stem cell identity. These distinct pathways have been elucidated mostly in Drosophila. Although the molecules involved are highly conserved in vertebrates, the way they act is tissue specific and sometimes very different from invertebrates.
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            Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin.

            Mutations in Pink1, a gene encoding a Ser/Thr kinase with a mitochondrial-targeting signal, are associated with Parkinson's disease (PD), the most common movement disorder characterized by selective loss of dopaminergic neurons. The mechanism by which loss of Pink1 leads to neurodegeneration is not understood. Here we show that inhibition of Drosophila Pink1 (dPink1) function results in energy depletion, shortened lifespan, and degeneration of select indirect flight muscles and dopaminergic neurons. The muscle pathology was preceded by mitochondrial enlargement and disintegration. These phenotypes could be rescued by the wild type but not the pathogenic C-terminal deleted form of human Pink1 (hPink1). The muscle and dopaminergic phenotypes associated with dPink1 inactivation show similarity to that seen in parkin mutant flies and could be suppressed by the overexpression of Parkin but not DJ-1. Consistent with the genetic rescue results, we find that, in dPink1 RNA interference (RNAi) animals, the level of Parkin protein is significantly reduced. Together, these results implicate Pink1 and Parkin in a common pathway that regulates mitochondrial physiology and cell survival in Drosophila.
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              The central complex and the genetic dissection of locomotor behaviour.

              The central complex is one of the most prominent, yet functionally enigmatic structures of the insect brain. Recently, behavioural, neuroanatomical and molecular approaches in Drosophila have joined forces to disclose specific components of higher locomotion control in larvae and adult flies, such as those that guarantee the optimal length and across-body symmetry of strides and an appropriate activity.
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                Author and article information

                Journal
                Neural Dev
                Neural Development
                BioMed Central
                1749-8104
                2011
                14 October 2011
                : 6
                : 34
                Affiliations
                [1 ]Institute of Medical Biology, 8A Biomedical Grove, Singapore 138648
                [2 ]Institute of Biotechnology, University of Helsinki, Viikinkaari 1, PO Box 65, Fin-00014 Finland
                [3 ]Bioinformatics Institute, 30 Biopolis Street, #07-01 Matrix, Singapore 138671
                Article
                1749-8104-6-34
                10.1186/1749-8104-6-34
                3206411
                21999236
                108a9bb9-6d2d-41aa-b79c-a8b4fbf8671e
                Copyright ©2011 Blanco et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 June 2011
                : 14 October 2011
                Categories
                Research Article

                Neurosciences
                Neurosciences

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