Abstract

Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal progenitor cells (RPCs) able to produce these cell types in a specific and timely order? Here, we will review the different models of retinal neurogenesis proposed over the last decades as well as the extrinsic and intrinsic factors controlling it. We will then focus on the molecular mechanisms, especially the cascade of transcription factors that regulate, more specifically, RGC fate. We will also comment on the recent discovery that the ciliary marginal zone is a new stem cell niche in mice contributing to retinal neurogenesis, especially to the generation of ipsilateral RGCs. Furthermore, RGCs are composed of many different subtypes that are anatomically, physiologically, functionally, and molecularly defined. We will summarize the different classifications of RGC subtypes and will recapitulate the specification of some of them and describe how a genetic disease such as albinism affects neurogenesis, resulting in profound visual deficits.

Highlights

  • IntroductionRetinal ganglion cells (RGCs) are the sole output neurons from the retina and integrate and transmit all visual information to the brain

  • Retinal ganglion cells (RGCs) are the sole output neurons from the retina and integrate and transmit all visual information to the brain. How are these RGCs generated during development? We will first review the main sequences of retinal neurogenesis, and how multipotent retinal progenitor cells (RPCs) can generate the seven retinal cell types

  • TFAP2D is a potential candidate found in the human retina, as it is a transcription factor expressed in RPCs and developing RGCs in the human retina from 5 gestational weeks [126], and is expressed in mouse retina from E13.5 to E16.5 [127]

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Summary

Introduction

Retinal ganglion cells (RGCs) are the sole output neurons from the retina and integrate and transmit all visual information to the brain. How are these RGCs generated during development? We will first review the main sequences of retinal neurogenesis, and how multipotent retinal progenitor cells (RPCs) can generate the seven retinal cell types.

Timing of RGC Neurogenesis
Extracellular Differentiation Signals
Sonic Hedgehog
Fibroblast Growth Factors
Competence and Stochastic Model of Retinal Cell Fate
Factors Controlling the Competence of Progenitors
Transcription Factors
Dlx Family of Transcription Factors
SoxC Family of Transcription Factors
Other Regulators
MicroRNA
Classification of RGC Subtypes
Morphological Criteria
Functional Criteria
Molecular Criteria
Brain Targeting
Pathfinding at the Optic Chiasm
10. Altered
Findings
11. Conclusions
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