Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body

  1. Najia A Elkahlah
  2. Jackson A Rogow
  3. Maria Ahmed
  4. E Josie Clowney  Is a corresponding author
  1. University of Michigan, United States
  2. The Rockefeller University, United States

Abstract

In order to represent complex stimuli, principle neurons of associative learning regions receive combinatorial sensory inputs. Density of combinatorial innervation is theorized to determine the number of distinct stimuli that can be represented and distinguished from one another, with sparse innervation thought to optimize the complexity of representations in networks of limited size. How the convergence of combinatorial inputs to principle neurons of associative brain regions is established during development is unknown. Here, we explore the developmental patterning of sparse olfactory inputs to Kenyon cells of the Drosophila melanogaster mushroom body. By manipulating the ratio between pre- and post-synaptic cells, we find that postsynaptic Kenyon cells set convergence ratio: Kenyon cells produce fixed distributions of dendritic claws while presynaptic processes are plastic. Moreover, we show that sparse odor responses are preserved in mushroom bodies with reduced cellular repertoires, suggesting that developmental specification of convergence ratio allows functional robustness.

Data availability

Analyzed data points generated during the study are included in the figures. Source data for Figure 7 is presented in a source data file.

Article and author information

Author details

  1. Najia A Elkahlah

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jackson A Rogow

    Laboratory of Neurophysiology and Behavior, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria Ahmed

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. E Josie Clowney

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States
    For correspondence
    jclowney@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9150-9464

Funding

Rita Allen Foundation (Milton Cassel Scholar)

  • E Josie Clowney

Alfred P. Sloan Foundation (Research Fellow in Neuroscience)

  • E Josie Clowney

University of Michigan (Startup Funds)

  • E Josie Clowney

University of Michigan (Neuroscience Scholar Award)

  • E Josie Clowney

Helen Hay Whitney Foundation (Simons Fellow)

  • E Josie Clowney

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claude Desplan, New York University, United States

Version history

  1. Received: September 28, 2019
  2. Accepted: January 7, 2020
  3. Accepted Manuscript published: January 8, 2020 (version 1)
  4. Version of Record published: February 18, 2020 (version 2)

Copyright

© 2020, Elkahlah 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.

Metrics

  • 3,913
    views
  • 590
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Najia A Elkahlah
  2. Jackson A Rogow
  3. Maria Ahmed
  4. E Josie Clowney
(2020)
Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body
eLife 9:e52278.
https://doi.org/10.7554/eLife.52278

Share this article

https://doi.org/10.7554/eLife.52278

Further reading

    1. Developmental Biology
    Zhimin Xu, Zhao Wang ... Yingchuan B Qi
    Research Article

    Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.

    1. Developmental Biology
    2. Structural Biology and Molecular Biophysics
    Samuel C Griffiths, Jia Tan ... Hsin-Yi Henry Ho
    Research Article Updated

    The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.