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      Temporal patterning of Drosophila medulla neuroblasts controls neural fates

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          Abstract

          In the Drosophila optic lobes, the medulla processes visual information coming from inner photoreceptors R7 and R8 and from lamina neurons. It contains ~40,000 neurons belonging to over 70 different types. We describe how precise temporal patterning of neural progenitors generates these different neural types. Five transcription factors--Homothorax, Eyeless, Sloppy-paired, Dichaete and Tailless--are sequentially expressed in a temporal cascade in each of the medulla neuroblasts as they age. Loss of either Eyeless, Sloppy-paired or Dichaete blocks further progression of the temporal sequence. We provide evidence that this temporal sequence in neuroblasts, together with Notch-dependent binary fate choice, controls the diversification of the neuronal progeny. Although a temporal sequence of transcription factors had been identified in Drosophila embryonic neuroblasts, our work illustrates the generality of this strategy, with different sequences of transcription factors being used in different contexts.

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          Most cited references41

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          Neuronal subtype specification in the cerebral cortex.

          In recent years, tremendous progress has been made in understanding the mechanisms underlying the specification of projection neurons within the mammalian neocortex. New experimental approaches have made it possible to identify progenitors and study the lineage relationships of different neocortical projection neurons. An expanding set of genes with layer and neuronal subtype specificity have been identified within the neocortex, and their function during projection neuron development is starting to be elucidated. Here, we assess recent data regarding the nature of neocortical progenitors, review the roles of individual genes in projection neuron specification and discuss the implications for progenitor plasticity.
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            Identification of functional elements and regulatory circuits by Drosophila modENCODE.

            To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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              Vertebrate neural cell-fate determination: lessons from the retina.

              Postmitotic neurons are produced from a pool of cycling progenitors in an orderly fashion during development. Studies of cell-fate determination in the vertebrate retina have uncovered several fundamental principles by which this is achieved. Most notably, a model for vertebrate cell-fate determination has been proposed that combines findings on the relative roles of extrinsic and intrinsic regulators in controlling cell-fate choices. At the heart of the model is the proposal that progenitors pass through intrinsically determined competence states, during which they are capable of giving rise to a limited subset of cell types under the influence of extrinsic signals.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                18 June 2013
                19 June 2013
                27 June 2013
                27 December 2013
                : 498
                : 7455
                : 456-462
                Affiliations
                Department of Biology, New York University, 100 Washington Square East, New York NY 10003, USA
                Author notes
                [* ]Correspondence and requests for materials should be addressed to C.D. ( cd38@ 123456nyu.edu )
                [1]

                Equal contribution

                [2]

                Present addresses: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032

                [3]

                Instituto de Neurociencias, CSIC, Universidad Miguel Hernández, Avenida Santiago Ramón y Cajal s/n, 03550 San Juan de Alicante, Spain.

                [4]

                Bogazici University, Department of Molecular Biology and Genetics, Kuzey Park Binasi 316, 34342 Bebek, Istanbul, Turkey

                Article
                NIHMS486188
                10.1038/nature12319
                3701960
                23783517
                0bc858ff-75d5-4422-a261-0eb0697bfc12

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Eye Institute : NEI
                Award ID: R01 EY017916 || EY
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