Reconciling competence and transcriptional hierarchies with stochasticity in retinal lineages - PubMed (original) (raw)

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Reconciling competence and transcriptional hierarchies with stochasticity in retinal lineages

Henrik Boije et al. Curr Opin Neurobiol. 2014 Aug.

Abstract

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?

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Figures

Figure 1

Figure 1

The competence model. The classical view sees retinal progenitor cells progressing through competence windows during which a particular cell type is generated (a). Recent studies suggest that although a unidirectional transition of competence occurs, progenitor cells choose from multiple fates at any one time (b).

Figure 2

Figure 2

Core transcriptional hierarchies. During the early proliferative phase of retinal development all RPCs express Vsx2, which inhibit factors such as Atoh7 and Vsx1. As development progress this inhibition is abolished and genes influencing cell fate are expressed. Depending on the level of Atoh7, and presence or not of Ptf1a, the progenitor follows different paths giving rise to different cell fates. The Vsx1-lineage gives rise to a distinct population of BCs from the population expressing Vsx2.

Figure 3

Figure 3

The complexity of transcriptional regulation. Although key factors can explain some the diversification there are numerous factors affecting fate outcome. Cross-talk between branches increase the complexity of the system.

Figure 4

Figure 4

Reconciliation. Stochastic models can predict the proliferative properties of RPCs, whether the daughter cells of RPCs continue to proliferate (P) or differentiate (D). In a similar way fate may be assigned in a stochastic way within a progression changing probabilities.

References

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