The Independent Probabilistic Firing of Transcription Factors: A Paradigm for Clonal Variability in the Zebrafish Retina.
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.
Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge CB2 3DY, UK; Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
Henrik
H
Boije
Department of Physics, Cambridge University, Cambridge CB3 0HE, UK.
Steffen
S
Rulands
Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge CB2 3DY, UK.
Stefanie
S
Dudczig
Department of Physics, Cambridge University, Cambridge CB3 0HE, UK.
Benjamin D
BD
Simons
Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge CB2 3DY, UK. Electronic address: wah20@cam.ac.uk.
William A
WA
Harris
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
D014157:Transcription Factors; D029961:Zebrafish Proteins