School of BioSciences - Research Publications

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Start date: 2009 × End date: 2009 × Author: Jusuf, Patricia ×

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    Vsx2 in the zebrafish retina: restricted lineages through derepression
    Vitorino, M ; Jusuf, PR ; Maurus, D ; Kimura, Y ; Higashijima, S-I ; Harris, WA (BMC, 2009-04-03)
    BACKGROUND: The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent. RESULTS: In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2. CONCLUSION: Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.
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    Ptf1a is expressed transiently in all types of amacrine cells in the embryonic zebrafish retina
    Jusuf, PR ; Harris, WA (BMC, 2009-09-04)
    BACKGROUND: The vertebrate retina is composed of five major types of neurons: three excitatory (photoreceptors, bipolar cells and ganglion cells) and two inhibitory (horizontal and amacrine cells). The transcription factor Ptf1a (pancreas transcription factor 1a) is important for the normal development of the inhibitory retinal neurons. RESULTS: Using a transgenic Ptf1a:GFP reporter and in situ hybridization in the zebrafish retina, we show that ptf1a message is transiently expressed in all amacrine and horizontal cells within hours after the terminal division of multipotent progenitors at the apical surface of the retinal neuroepithelium, and remains on as these cells migrate to their final laminar location. The message then shuts off, but we can follow the stable Ptf1a:GFP protein for up to 120 hours post-fertilization. A variety of anatomically and neurochemically distinct subtypes of amacrine cells can already be distinguished at this embryonic time point. CONCLUSION: The timing of Ptf1a expression suggests that it is involved in the very early stages or steps in the differentiation of amacrine cells, which, due to the perdurance of the Ptf1a:GFP, can be seen to rapidly diversify into a large number of subtypes. This work sets the stage for future studies looking at genetic specification of amacrine subtypes.