1. Developmental Biology
Download icon

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

  1. Elisa Nerli
  2. Mauricio Rocha-Martins
  3. Caren Norden  Is a corresponding author
  1. MPI of Molecular Cell Biology and Genetics, Germany
Research Article
  • Cited 2
  • Views 1,808
  • Annotations
Cite this article as: eLife 2020;9:e60462 doi: 10.7554/eLife.60462


During brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitor divisions that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting its suitability for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry, as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly however, Notch does not act through an apicobasal activity gradient as previously suggested, but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate progenitor state exists in the retina. Our study thus reveals new insights into the regulation of proliferative and differentiative events during central nervous system development.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures for which necessary.

Article and author information

Author details

  1. Elisa Nerli

    MPI of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Mauricio Rocha-Martins

    MPI of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Caren Norden

    MPI of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8835-1451


ERC consolidator grant (H2020 ERC-2018-CoG-81904)

  • Caren Norden

Deutsche Forschungsgemeinschaft (NO 1068/5-1)

  • Caren Norden


  • Caren Norden

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


Animal experimentation: All animal work in this study was performed in accordance with European Union directive 2010/63/EU, as well as the German Animal Welfare Act.

Reviewing Editor

  1. Tatjana Piotrowski, Stowers Institute for Medical Research, United States

Publication history

  1. Received: June 26, 2020
  2. Accepted: November 2, 2020
  3. Accepted Manuscript published: November 3, 2020 (version 1)
  4. Version of Record published: November 20, 2020 (version 2)


© 2020, Nerli 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.


  • 1,808
    Page views
  • 255
  • 2

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)

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

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

Further reading

    1. Developmental Biology
    Jody A Summers, Elizabeth Martinez
    Research Article Updated

    Postnatal ocular growth is regulated by a vision-dependent mechanism that acts to minimize refractive error through coordinated growth of the ocular tissues. Of great interest is the identification of the chemical signals that control visually guided ocular growth. Here, we provide evidence that the pro-inflammatory cytokine, interleukin-6 (IL-6), may play a pivotal role in the control of ocular growth using a chicken model of myopia. Microarray, real-time RT-qPCR, and ELISA analyses identified IL-6 upregulation in the choroids of chick eyes under two visual conditions that introduce myopic defocus and slow the rate of ocular elongation (recovery from induced myopia and compensation for positive lenses). Intraocular administration of atropine, an agent known to slow ocular elongation, also resulted in an increase in choroidal IL-6 gene expression. Nitric oxide appears to directly or indirectly upregulate choroidal IL-6 gene expression, as administration of the non-specific nitric oxide synthase inhibitor, L-NAME, inhibited choroidal IL-6 gene expression, and application of a nitric oxide donor stimulated IL-6 gene and protein expression in isolated chick choroids. Considering the pleiotropic nature of IL-6 and its involvement in many biological processes, these results suggest that IL-6 may mediate many aspects of the choroidal response in the control of ocular growth.

    1. Developmental Biology
    2. Genetics and Genomics
    Juliet R Girard et al.
    Research Article Updated

    Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.