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

During brain development, progenitor cells need to balanceproliferation 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...

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Main Authors: Elisa Nerli, Mauricio Rocha-Martins, Caren Norden
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/60462
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author Elisa Nerli
Mauricio Rocha-Martins
Caren Norden
author_facet Elisa Nerli
Mauricio Rocha-Martins
Caren Norden
author_sort Elisa Nerli
collection DOAJ
description During brain development, progenitor cells need to balanceproliferation 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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spelling doaj.art-a8aeb3f98235463d9dbed438a01236cf2022-12-22T03:52:40ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.60462Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathwayElisa Nerli0https://orcid.org/0000-0003-4204-9702Mauricio Rocha-Martins1Caren Norden2https://orcid.org/0000-0001-8835-1451Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Instituto Gulbenkian de Ciência, Oeiras, PortugalMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Instituto Gulbenkian de Ciência, Oeiras, PortugalMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Instituto Gulbenkian de Ciência, Oeiras, PortugalDuring brain development, progenitor cells need to balanceproliferation 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.https://elifesciences.org/articles/60462quantitative live-imagingretinal developmentfate asymmetryNotchSara endosomes
spellingShingle Elisa Nerli
Mauricio Rocha-Martins
Caren Norden
Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
eLife
quantitative live-imaging
retinal development
fate asymmetry
Notch
Sara endosomes
title Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
title_full Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
title_fullStr Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
title_full_unstemmed Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
title_short Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway
title_sort asymmetric neurogenic commitment of retinal progenitors involves notch through the endocytic pathway
topic quantitative live-imaging
retinal development
fate asymmetry
Notch
Sara endosomes
url https://elifesciences.org/articles/60462
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AT mauriciorochamartins asymmetricneurogeniccommitmentofretinalprogenitorsinvolvesnotchthroughtheendocyticpathway
AT carennorden asymmetricneurogeniccommitmentofretinalprogenitorsinvolvesnotchthroughtheendocyticpathway