Apoptosis-induced self-renewal of neurogenic progenitors safeguards retinal development against extensive cell loss

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Developing embryos have a striking ability to buffer external and internal perturbations. A key example of this phenomenon across developing systems is successful organ formation even after substantial cell loss. Although molecular regulators of this robustness are beginning to be understood, it remains unclear whether and how surviving cells can remodel their developmental trajectories to safeguard morphogenesis. To address this question, we use the zebrafish retina, where progenitor behaviour and lineage transitions are highly tractable and extensively characterized. We induce widespread apoptosis via heat stress and genetic approaches and track cellular and tissue-wide responses in vivo over time. We find that retinal development is highly resilient with neurogenesis initiating on time and growth continuing despite extensive apoptosis. Continued growth is supported by neurogenic progenitors that react to apoptosis through a non-cell autonomous switch in behaviour. These cells bypass their canonical differentiation route and undergo self-renewing divisions that expand clonal output and compensate for lost cells. Importantly, self-renewal is transient, progenitors resume lineage progression, generating appropriate neuronal cell types. This adaptive response supports the formation of retinas with proper architecture, connectivity to the brain and visual function. Together, these findings identify latent plasticity in the neurogenic programme as a mechanism that contributes to developmental robustness under stress.

Article activity feed