How Variable Clones Build an Invariant Retina

Abstract

SummaryA fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle.

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

“…By contrast, miR-720 was one of the few miRNAs not reduced in the Dicer-CKO, suggesting either that this miRNA is very stable, or that it is processed independently of Dicer; in either case, it is unlikely to contribute to the Dicer-CKO phenotype. We also did not analyze miR-106b further because a prior analysis of combined deletion of miR106b and miR106a loci did not report a significant defect in eye development (13).…”

Photoreceptor cell fate specification in vertebrates

“…However, this is not always the case; it has been known for many years that teleost fish (e.g. zebrafish and goldfish) possess a progenitor that is restricted to producing only rod photoreceptors, although this has been considered an adaptation to maintain light sensitivity and rod density as the retina grows in postembryonic stages (Raymond and Rivlin, 1987), and more recent studies have provided evidence for horizontal-and cone-restricted progenitors in fish (Godinho et al, 2007;He et al, 2012;Suzuki et al, 2013). Together, these studies suggest that many of the specification events leading to the generation of photoreceptors, and even their specific subtype, can occur in either proliferative progenitor or postmitotic precursor (see Glossary, Box 1) cells.…”

“…This is because in lineagetracing studies two-cell clones derived from Olig2 + , Neurog2 + and Ascl1 + progenitors sometimes contain two photoreceptors and sometimes a photoreceptor and a non-photoreceptor type (Brzezinski et al, 2011;Hafler et al, 2012). Live imaging experiments in zebrafish show that terminal divisions can generate similar diversity, although there are also lineage-restricted cone and rod progenitors (Godinho et al, 2007;He et al, 2012;Suzuki et al, 2013). These results imply that the specification events that define rod and cone fates are not strictly linked to the status of the cell cycle.…”

Dynamic clonal analysis based on chronic in vivo imaging allows multiscale quantification of growth in the Drosophila wing disc

“…Until now, the most accurate characterizationin the mouse limb bud -assessed growth from landmarks on the external envelope of the tissue and required ex vivo culture, with the limitation on growth sustainability discussed above. Zebrafish was used recently to analyze cleavage of the early embryo (Olivier et al, 2010) and proliferation of the growing retina (He et al, 2012). Although the former did not specifically investigate a growing tissue and the latter did not investigate shape changes, these studies Fig.…”