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      Influences on neural lineage and mode of division in the zebrafish retina in vivo

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          Abstract

          Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156–160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15–26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142–1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide along the central-peripheral axis and produce two RGCs. This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

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          Most cited references48

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          Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis.

          Neurons in the mammalian central nervous system are generated from progenitor cells near the lumen of the neural tube. Time-lapse microscopy of dividing cells in slices of developing cerebral cortex reveals that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool. In contrast, horizontally dividing cells produce basal daughters that behave like young migratory neurons and apical daughters that remain within the proliferative zone. Notch1 immunoreactivity is distributed asymmetrically in mitotic cells, with Notch1 inherited selectively by the basal (neuronal) daughter of horizontal divisions. These results provide cellular and molecular evidence that cortical neurons are generated from asymmetric divisions.
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            Requirement for math5 in the development of retinal ganglion cells.

            math5 is a murine orthologue of atonal, a bHLH proneural gene essential for the formation of photoreceptors and chordotonal organs in Drosophila. The expression of math5 coincides with the onset of retinal ganglion cell (RGC) differentiation. Targeted deletion of math5 blocks the initial differentiation of 80% of RGCs and results in an increase in differentiated amacrine cells. Furthermore, the absence of math5 abolishes the retinal expression of brn-3b and the formation of virtually all brn-3b-expressing RGCs. These results imply that math5 is a proneural gene essential for RGC differentiation and that math5 acts upstream to activate brn-3b-dependent differentiation processes in RGCs.
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              Retinal ganglion cell genesis requires lakritz, a Zebrafish atonal Homolog.

              Mutation of the zebrafish lakritz (lak) locus completely eliminates the earliest-born retinal cells, the ganglion cells (RGCs). Instead, excess amacrine, bipolar, and Müller glial cells are generated in the mutant. The extra amacrines are found at ectopic locations in the ganglion cell layer. Cone photoreceptors appear unaffected by the mutation. Molecular analysis reveals that lak encodes Ath5, the zebrafish eye-specific ortholog of the Drosophila basic helix-loop-helix transcription factor Atonal. A combined birth-dating and cell marker analysis demonstrates that lak/ath5 is essential for RGC determination during the first wave of neurogenesis in the retina. Our results suggest that this wave is skipped in the mutant, leading to an accumulation of progenitors for inner nuclear layer cells.
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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                19 December 2005
                : 171
                : 6
                : 991-999
                Affiliations
                [1 ]Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom
                [2 ]RIKEN Institute of Physical and Chemical Research, Hirosawa, Saitama 351-0198, Japan
                Author notes

                Correspondence to William A. Harris: harris@ 123456mole.bio.cam.ac.uk

                Article
                200509098
                10.1083/jcb.200509098
                2171316
                16365165
                bb3def36-f7d0-43c2-bb20-edf9cc20cbb4
                Copyright © 2005, The Rockefeller University Press
                History
                : 16 September 2005
                : 14 November 2005
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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