title: The ciliary marginal zone of the zebrafish retina: clonal and time-lapse analysis of a continuously growing tissue.
abstract: Clonal analysis is helping us understand the dynamics of cell replacement in homeostatic adult tissues (Simons and Clevers, 2011). Such an analysis, however, has not yet been achieved for continuously growing adult tissues, but is essential if we wish to understand the architecture of adult organs. The retinas of lower vertebrates grow throughout life from retinal stem cells (RSCs) and retinal progenitor cells (RPCs) at the rim of the retina, called the ciliary marginal zone (CMZ). Here, we show that RSCs reside in a niche at the extreme periphery of the CMZ and divide asymmetrically along a radial (peripheral to central) axis, leaving one daughter in the peripheral RSC niche and the other more central where it becomes an RPC. We also show that RPCs of the CMZ have clonal sizes and compositions that are statistically similar to progenitor cells of the embryonic retina and fit the same stochastic model of proliferation. These results link embryonic and postembryonic cell behaviour, and help to explain the constancy of tissue architecture that has been generated over a lifetime.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA 20147, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Almeida
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rulands
authors.affiliation: Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Naima
authors.initials: N
authors.lastname: Chalour
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Muresan
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Yunmin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK wah20@cam.ac.uk.
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D012160:Retina / Q000166:cytology* / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish / Q000254:growth & development*
keywords: Ciliary marginal zone; Clonal analysis; Live imaging; Progenitor cells; Retina; Stem cells; Zebrafish