The Independent Probabilistic Firing of Transcription Factors: A Paradigm for Clonal Variability in the Zebrafish Retina.
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Authors
Boije, Henrik
Rulands, Steffen https://orcid.org/0000-0001-6398-1553
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
1878-1551
Volume Title
34
Publisher
Elsevier BV
Publisher DOI
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (100329/Z/12/Z)
Wellcome Trust (092096/Z/10/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).