How Variable Clones Build an Invariant Retina

• Published in: Neuron (Cambridge, Mass.) Vol. 75; no. 5; pp. 786 - 798
• Main Authors: He, Jie, Zhang, Gen, Almeida, Alexandra D., Cayouette, Michel, Simons, Benjamin D., Harris, William A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2012; Elsevier Limited; Cell Press
• Subjects: Animals; Animals, Genetically Modified; Cell cycle; Cell division; Cell Lineage - genetics; Clone Cells; Cloning; Danio rerio; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - embryology; Freshwater; Gene expression; Monte Carlo simulation; Nervous system; Neurons; Organogenesis - physiology; Retina; Retina - cytology; Retina - embryology; Retinal Neurons - cytology; Retinal Neurons - physiology; Stem Cells - cytology; Stem Cells - physiology; Studies; Transcription factors; Trees; Zebrafish
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2012.06.033

A 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. ► Method for full live lineage tracing of retinal cells in vivo ► Demonstration that retinal clone growth is representative of retinal growth ► A stochastic model accurately predicts clone growth from equipotent progenitors ► Links between mode of cell division and cell fate help explain histogenesis A key question in developmental neuroscience is how a collection of progenitors proliferates and differentiates to create a brain of the consistent size and composition. He et al. use lineage tracing to reconstruct the full retinal lineages in vivo and propose a model for stochastic control of lineage progression.