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

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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.

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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

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Elisa Nerli

MPI of Molecular Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.
Mauricio Rocha-Martins

MPI of Molecular Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.
Caren Norden

MPI of Molecular Cell Biology and Genetics, Dresden, Germany

For correspondence
cnorden@igc.gulbenkian.pt

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8835-1451

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.

Copyright

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.