Differentiation signals from glia are fine-tuned to set neuronal numbers during development

Abstract

Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the 'extra' precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xgO), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to EGF from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the 'extra' precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xgO differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the 'extra' precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuron

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All data generated or analysed during this study are included in the manuscript

Article and author information

Author details

  1. Anadika R Prasad

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Inês Lago-Baldaia

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  3. Matthew P Bostock

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Zaynab Housseini

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Vilaiwan M Fernandes

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    For correspondence
    vilaiwan.fernandes@ucl.ac.uk
    Competing interests
    Vilaiwan M Fernandes, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1991-7252

Funding

Wellcome Trust (210472/Z/18/Z)

  • Vilaiwan M Fernandes

UCL Overseas Research Scholarship

  • Anadika R Prasad

UCL Graduate Research Scholarship

  • Anadika R Prasad

UCL Biosciences Graduate Research Scholarship

  • Matthew P Bostock

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

Copyright

© 2022, Prasad 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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  1. Anadika R Prasad
  2. Inês Lago-Baldaia
  3. Matthew P Bostock
  4. Zaynab Housseini
  5. Vilaiwan M Fernandes
(2022)
Differentiation signals from glia are fine-tuned to set neuronal numbers during development
eLife 11:e78092.
https://doi.org/10.7554/eLife.78092

Share this article

https://doi.org/10.7554/eLife.78092

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