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Temporal patterning of Drosophila medulla neuroblasts controls neural fates

Nature volume 498, pages 456–462 (2013)Cite this article

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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 approximately 40,000 neurons belonging to more than 70 different types. Here 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 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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Figure 1: The developing medulla.
Figure 2: A temporal sequence of transcription factors in medulla neuroblasts.
Figure 3: Cross-regulations between transcription factors in the gene cascade.
Figure 4: Notch-dependent asymmetric division of medulla GMCs.
Figure 5: Hth and Ey are required for neuronal diversity.
Figure 6: Slp is required for neuronal diversity.

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Acknowledgements

We thank the fly community and the modENCODE team for gifts of antibodies and fly stocks. K. White, N. Negre, D. Vasiliauskas and R. Johnston contributed to screening the modENCODE antibodies. Special thanks to C.-H. Lee for sharing unpublished information and the OrtC1-gal4 line. We thank R. Mann for suggestions and reagents; and Desplan laboratory members for discussion and support, especially R. Johnston, D. Vasiliauskas and N. Neriec for critically reading the manuscript. This work was supported by National Institutes of Health (NIH) grant R01 Ey017916 to C.D.; The Robert Leet and Clara Guthrie Patterson Trust Postdoctoral Fellowship to X.L.; The Canadian Institutes of Health Research (CIHR) to T.E.; fellowships from EMBO (ALTF 680-2009) and HFSPO (LT000077/2010-L) to C.B.; NIH grant GM058575 and a Career Development fellowship from the Leukemia and Lymphoma Society to R.V.

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Author notes

  1. Javier Morante & Arzu Celik

    Present address: Present addresses: Instituto de Neurociencias, CSIC, Universidad Miguel Hernández, Avenida Santiago Ramón y Cajal s/n, 03550 San Juan de Alicante, Spain (J.M.); Bogazici University, Department of Molecular Biology and Genetics, Kuzey Park Binasi 316, 34342 Bebek, Istanbul, Turkey (A.C.).,

  2. Xin Li and Ted Erclik: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, New York University, 100 Washington Square East, New York, New York 10003, USA,

    Xin Li, Ted Erclik, Claire Bertet, Zhenqing Chen, Srinidhi Venkatesh, Javier Morante, Arzu Celik & Claude Desplan

  2. Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA,

    Roumen Voutev

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Contributions

C.D. planned the project and analysed the data together with X.L. and T.E.; T.E., X.L. and C.B. performed the antibody screen; X.L. conducted experiments with Hth, Ey, Slp and Tll neuroblasts as well as Ap and the Notch pathway; T.E. analysed the D neuroblasts; Z.C. generated the OrtC1-gal4 flip-out and MARCM clones; R.V. generated the ey BAC rescue construct and stocks; S.V. examined Slp2 expression; A.C. identified the AC225-gal4 line and J.M. defined its expression in the transition from neuroepithelium to neuroblast. The manuscript was written by X.L. and C.D., and all authors commented on it.

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Correspondence to Claude Desplan.

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Li, X., Erclik, T., Bertet, C. et al. Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature 498, 456–462 (2013). https://doi.org/10.1038/nature12319

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