Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution

Sarah K. Rempel; Madalynn J. Welch; Allison L. Ludwig; M. Joseph Phillips; Yochana Kancherla; Donald J. Zack; David M. Gamm; Timothy M. Gómez

Cell Reports (May 2022)

Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution

Sarah K. Rempel,
Madalynn J. Welch,
Allison L. Ludwig,
M. Joseph Phillips,
Yochana Kancherla,
Donald J. Zack,
David M. Gamm,
Timothy M. Gómez

Affiliations

Sarah K. Rempel: Department of Neuroscience, University of Wisconsin – Madison, Madison, WI 53706, USA; McPherson Eye Research Institute, University of Wisconsin – Madison, Madison, WI 53706, USA
Madalynn J. Welch: Department of Neuroscience, University of Wisconsin – Madison, Madison, WI 53706, USA
Allison L. Ludwig: Department of Ophthalmology and Visual Sciences, University of Wisconsin – Madison, Madison, WI 53705, USA; McPherson Eye Research Institute, University of Wisconsin – Madison, Madison, WI 53706, USA; Waisman Center, University of Wisconsin – Madison, Madison, WI 53705, USA
M. Joseph Phillips: McPherson Eye Research Institute, University of Wisconsin – Madison, Madison, WI 53706, USA; Waisman Center, University of Wisconsin – Madison, Madison, WI 53705, USA
Yochana Kancherla: Department of Neuroscience, University of Wisconsin – Madison, Madison, WI 53706, USA
Donald J. Zack: Department of Ophthalmology, Johns Hopkins University, Baltimore, MD 21287, USA
David M. Gamm: Department of Ophthalmology and Visual Sciences, University of Wisconsin – Madison, Madison, WI 53705, USA; McPherson Eye Research Institute, University of Wisconsin – Madison, Madison, WI 53706, USA; Waisman Center, University of Wisconsin – Madison, Madison, WI 53705, USA
Timothy M. Gómez: Department of Neuroscience, University of Wisconsin – Madison, Madison, WI 53706, USA; McPherson Eye Research Institute, University of Wisconsin – Madison, Madison, WI 53706, USA; Corresponding author

Journal volume & issue: Vol. 39, no. 7
p. 110827

Abstract

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Summary: Photoreceptors (PRs) are the primary visual sensory cells, and their loss leads to blindness that is currently incurable. Although cell replacement therapy holds promise, success is hindered by our limited understanding of PR axon growth during development and regeneration. Here, we generate retinal organoids from human pluripotent stem cells to study the mechanisms of PR process extension. We find that early-born PRs exhibit autonomous axon extension from dynamic terminals. However, as PRs age from 40 to 80 days of differentiation, they lose dynamic terminals on 2D substrata and in 3D retinal organoids. Interestingly, PRs without motile terminals are still capable of extending axons but only by process stretching via attachment to motile non-PR cells. Immobile PR terminals of late-born PRs have fewer and less organized actin filaments but more synaptic proteins compared with early-born PR terminals. These findings may help inform the development of PR transplantation therapies.

CP: Neuroscience

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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