1. Developmental Biology
  2. Neuroscience
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Glial and neuronal Semaphorin signaling instruct the development of a functional myotopic map for Drosophila walking

  1. Durafshan Sakeena Syed
  2. Swetha BM
  3. O Venkateswara Reddy
  4. Heinrich Reichert
  5. K VijayRaghavan  Is a corresponding author
  1. Tata Institute of Fundamental Research, India
  2. University of Basel, Switzerland
Research Article
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Cite this article as: eLife 2016;5:e11572 doi: 10.7554/eLife.11572

Abstract

Motoneurons developmentally acquire appropriate cellular architectures that ensure connections with postsynaptic muscles and presynaptic neurons. In Drosophila, leg motoneurons are organized as a myotopic map, where their dendritic domains represent the muscle field. Here we investigate mechanisms underlying development of aspects of this myotopic map, required for walking. A behavioral screen identified roles for Semaphorins (Sema) and Plexins (Plex) in walking behavior. Deciphering this phenotype, we show that PlexA/Sema1a mediates motoneuron axon branching in ways that differ in the proximal femur and distal tibia, based on motoneuronal birth order. Importantly, we show a novel role for glia in positioning dendrites of specific motoneurons; PlexB/Sema2a is required for dendritic positioning of late-born motoneurons but not early-born motoneurons. These findings indicate that communication within motoneurons and between glia and motoneurons, mediated by the combined action of different Plexin/Semaphorin signaling systems, are required for the formation of a functional myotopic map.

Article and author information

Author details

  1. Durafshan Sakeena Syed

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
  2. Swetha BM

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
  3. O Venkateswara Reddy

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
  4. Heinrich Reichert

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    No competing interests declared.
  5. K VijayRaghavan

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    For correspondence
    vijay@ncbs.res.in
    Competing interests
    K VijayRaghavan, Senior editor, eLife.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Publication history

  1. Received: September 12, 2015
  2. Accepted: February 28, 2016
  3. Accepted Manuscript published: February 29, 2016 (version 1)
  4. Version of Record published: March 14, 2016 (version 2)

Copyright

© 2016, Syed et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-Associated Protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the Collapsin Response Mediator Protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within Detergent-Resistant Membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E's growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

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