1. Developmental Biology
  2. Neuroscience

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

  1. Anadika R Prasad
  2. Inês Lago-Baldaia
  3. Matthew P Bostock
  4. Zaynab Housseini
  5. Vilaiwan M Fernandes  Is a corresponding author
  1. University College London, United Kingdom
https://doi.org/10.7554/eLife.78092
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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
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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

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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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Further reading

    1. Developmental Biology
    2. Neuroscience

    Photoreceptors generate neuronal diversity in their target field through a Hedgehog morphogen gradient in Drosophila

    Matthew P Bostock, Anadika R Prasad ... Vilaiwan M Fernandes
    Research Article Updated

    Defining the origin of neuronal diversity is a major challenge in developmental neurobiology. The Drosophila visual system is an excellent paradigm to study how cellular diversity is generated. Photoreceptors from the eye disc grow their axons into the optic lobe and secrete Hedgehog (Hh) to induce the lamina, such that for every unit eye there is a corresponding lamina unit made up of post-mitotic precursors stacked into columns. Each differentiated column contains five lamina neuron types (L1-L5), making it the simplest neuropil in the optic lobe, yet how this diversity is generated was unknown. Here, we found that Hh pathway activity is graded along the distal-proximal axis of lamina columns, and further determined that this gradient in pathway activity arises from a gradient of Hh ligand. We manipulated Hh pathway activity cell autonomously in lamina precursors and non-cell autonomously by inactivating the Hh ligand and by knocking it down in photoreceptors. These manipulations showed that different thresholds of activity specify unique cell identities, with more proximal cell types specified in response to progressively lower Hh levels. Thus, our data establish that Hh acts as a morphogen to pattern the lamina. Although this is the first such report during Drosophila nervous system development, our work uncovers a remarkable similarity with the vertebrate neural tube, which is patterned by Sonic Hh. Altogether, we show that differentiating neurons can regulate the neuronal diversity of their distant target fields through morphogen gradients.