Abstract
The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post‐fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis.
Highlights
The nervous system is principally made up of neurons and glia
Our data suggest that each Retinal Progenitor Cell (RPC) in the undifferentiated 24 hpf optic cup is predestined to give rise to one, and only one, Müller cell (MC)
Besides the striking similarity between the average size of a clone generated by a 24 hpf RPC (22.3 cells, Boije et al, 2015) and the ratio of MCs in the differentiated retina (1 in 22.6 cells), we show, through clonal analysis, a strong correlation between the RPCs of the optic cup and MCs in the mature retina
Summary
The nervous system is principally made up of neurons and glia. There are still many unanswered questions regarding how proliferation is controlled, how fates are assigned, and the potency of different progenitors. Multipotent retinal progenitor cells (RPCs) in the optic cup proliferate and differentiate into five types of neurons and one type of glia, the Müller cell (MC; Boije, MacDonald, & Harris, 2014; Masland, 2001). All peer review communications can be found with the online version of the article. We found that individual RPCs in the 24 hrs post-fertilization (hpf) optic cup generate exactly one MC in the vast majority of clones, independently of the overall clone size. This reveals a double nature of retinal lineages where both stochastic and deterministic traits govern clonal development
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