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
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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

Data availability

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.

Reviewing Editor

  1. Sonia Sen, Tata Institute for Genetics and Society, India

Version history

  1. Preprint posted: December 14, 2021 (view preprint)
  2. Received: February 22, 2022
  3. Accepted: September 11, 2022
  4. Accepted Manuscript published: September 12, 2022 (version 1)
  5. Version of Record published: September 23, 2022 (version 2)

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.

Metrics

  • 1,382
    Page views
  • 259
    Downloads
  • 2
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. 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

Categories and tags

Research organism

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.

    1. Developmental Biology

    Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans

    Taylor N Medwig-Kinney, Brian A Kinney ... David Q Matus
    Research Article

    A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of NHR-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which the association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.

    1. Chromosomes and Gene Expression
    2. Developmental Biology

    Transcription: A hub of activity

    Virginia L Pimmett, Mounia Lagha
    Insight

    Imaging experiments reveal the complex and dynamic nature of the transcriptional hubs associated with Notch signaling.