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

Elisa Nerli,Caren Norden,Mauricio Rocha-Martins

doi:10.7554/elife.60462

Abstract

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.

Highlights

During central nervous system (CNS) development in vertebrates, the balance between proliferation and differentiation is crucial to generate the different types of neurons in the correct numbers and proportions
Ath5 positive neurogenic progenitors arise from asymmetric divisions
To understand how neurogenic progenitors emerge from multipotent progenitors in the developing zebrafish retina, we asked how the earliest of these neurogenic progenitors arise

Summary

Introduction

During central nervous system (CNS) development in vertebrates, the balance between proliferation and differentiation is crucial to generate the different types of neurons in the correct numbers and proportions. This in turn ensures functionality of the neural tissue as it is the prerequisite for correct neuronal connectivity and circuit formation. Multipotent progenitors are key to maintain this balance They first increase in number through a phase of active proliferation (Fish et al, 2006; Homem et al, 2015) which is followed by neurogenesis onset. Understanding the parameters that differ between cells primed for continued proliferation versus cells that enter the neurogenic program is of utmost importance to comprehend brain development in health and disease

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