A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology

  1. Jérôme Lacoste  Is a corresponding author
  2. Hédi Soula
  3. Angélique Burg
  4. Agnès Audibert
  5. Pénélope Darnat
  6. Michel Gho  Is a corresponding author
  7. Sophie Louvet-Vallée  Is a corresponding author
  1. CNRS Sorbonne-Université, France
  2. Sorbonne Université, INSERM, France

Abstract

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, an anteromedial located central SOP divides first, then neighbouring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. Furthermore, when this mitotic wave was reduced, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behaviour was impaired. We show that the temporal order of progenitor divisions influences the birth order of sensory neurons, axon branching and impact on grooming behaviour. These data support the idea that developmental timing controls axon wiring neural diversity.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jérôme Lacoste

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    For correspondence
    jerome.lacoste@sorbonne-universite.fr
    Competing interests
    The authors declare that no competing interests exist.
  2. Hédi Soula

    NutriOmics Research Unit, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Angélique Burg

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Agnès Audibert

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Pénélope Darnat

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Michel Gho

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    For correspondence
    michel.gho@sorbonne-universite.fr
    Competing interests
    The authors declare that no competing interests exist.
  7. Sophie Louvet-Vallée

    UMR 7622 laboratory of Developmental Biology, CNRS Sorbonne-Université, Paris, France
    For correspondence
    sophie.louvet_vallee@sorbonne-universite.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7577-2329

Funding

Funding was provided by recurrent subsides from the Centre National de la Recherche Scientifique and the Sorbonne University. No external funding was receives for this work.

Copyright

© 2022, Lacoste 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

  • 795
    views
  • 110
    downloads
  • 7
    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. Jérôme Lacoste
  2. Hédi Soula
  3. Angélique Burg
  4. Agnès Audibert
  5. Pénélope Darnat
  6. Michel Gho
  7. Sophie Louvet-Vallée
(2022)
A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology
eLife 11:e75746.
https://doi.org/10.7554/eLife.75746

Share this article

https://doi.org/10.7554/eLife.75746

Further reading

    1. Cell Biology
    2. Genetics and Genomics
    Keva Li, Nicholas Tolman ... UK Biobank Eye and Vision Consortium
    Research Article

    A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve = 0.579), they offered marginal prediction improvement in PRS-only-based models (p=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites—lactate (p=8.8E-12), pyruvate (p=1.9E-10), and citrate (p=0.02)—linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (Pinteraction = 0.011). Higher total resilience metabolite levels within the highest PRS quartile corresponded to lower glaucoma prevalence (Odds Ratiohighest vs. lowest total resilience metabolite quartile=0.71, 95% Confidence Interval = 0.64–0.80). As pyruvate is a foundational metabolite linking glycolysis to tricarboxylic acid cycle metabolism and ATP generation, we pursued experimental validation for this putative resilience biomarker in a human-relevant Mus musculus glaucoma model. Dietary pyruvate mitigated elevated intraocular pressure (p=0.002) and optic nerve damage (p<0.0003) in Lmx1bV265D mice. These findings highlight the protective role of pyruvate-related metabolism against glaucoma and suggest potential avenues for therapeutic intervention.

    1. Cell Biology
    2. Immunology and Inflammation
    Alejandro Rosell, Agata Adelajda Krygowska ... Esther Castellano Sanchez
    Research Article

    Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.