Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
Abstract
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
Funding
ERC consolidator grant (H2020 ERC-2018-CoG-81904)
- Caren Norden
Deutsche Forschungsgemeinschaft (NO 1068/5-1)
- Caren Norden
Max-Planck-Gesellschaft
- Caren Norden
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
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
- Tatjana Piotrowski, Stowers Institute for Medical Research, United States
Version history
- Received: June 26, 2020
- Accepted: November 2, 2020
- Accepted Manuscript published: November 3, 2020 (version 1)
- Version of Record published: November 20, 2020 (version 2)
Copyright
© 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.
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Further reading
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- Chromosomes and Gene Expression
- Developmental Biology
Imaging experiments reveal the complex and dynamic nature of the transcriptional hubs associated with Notch signaling.
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- Cell Biology
- Developmental Biology
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