Reconciling competence and transcriptional hierarchies with stochasticity in retinal lineages.
Bottom Line: Recent advances suggest that there is a stochastic contribution to the proliferation and fate choice of retinal progenitors.How does this stochasticity fit with the progression of temporal competence and the transcriptional hierarchies that also influence cell division and cell fate in the developing retina?Where may stochasticity arise in the system and how do we make progress in this field when we may never fully explain the behavior of individual progenitor cells?
Affiliation: Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, UK.Show MeSH
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Mentions: While this core hierarchy may explain how the major cell types arise, a number of studies, too many to review here, have revealed that several additional factors that also influence particular retinal fates (Figure 3, revised from ). Moreover, the simultaneous expression of two or more TFs can synergistically influence fate suggesting that combinatorial coding also plays an influential role cell fate diversification [32–34]. From these studies, it appears that the intrinsic core hierarchy of retinal cell determination is overlaid with a complex weave of transcriptional circuitry that makes it challenging to predict which cell types will arise from particular progenitors.
Affiliation: Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, UK.