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The Independent Probabilistic Firing of Transcription Factors: A Paradigm for Clonal Variability in the Zebrafish Retina.


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Authors

Boije, Henrik 
Dudczig, Stefanie 
Simons, Benjamin D 
Harris, William A 

Abstract

Early retinal progenitor cells (RPCs) in vertebrates produce lineages that vary greatly both in terms of cell number and fate composition, yet how this variability is achieved remains unknown. One possibility is that these RPCs are individually distinct and that each gives rise to a unique lineage. Another is that stochastic mechanisms play upon the determinative machinery of equipotent early RPCs to drive clonal variability. Here we show that a simple model, based on the independent firing of key fate-influencing transcription factors, can quantitatively account for the intrinsic clonal variance in the zebrafish retina and predict the distributions of neuronal cell types in clones where one or more of these fates are made unavailable.

Description

Keywords

Animals, Cell Differentiation, Cell Lineage, Gene Expression Regulation, Developmental, Retina, Stem Cells, Transcription Factors, Zebrafish, Zebrafish Proteins

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

34

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (100329/Z/12/Z)
Wellcome Trust (092096/Z/10/Z)
BDS and SR acknowledge the support of the Wellcome Trust (098357/Z/12/Z). WAH and HB also acknowledge the support of the Wellcome Trust (100329/Z/12/Z). HB was also supported by the Swedish Research Council (2011-7054).