Abstract
BackgroundThe 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.ResultsIn 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.ConclusionOur 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.
Highlights
The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs)
We show that Vsx2 is present in all early RPCs, but turns off in most cells as retinogenesis proceeds, remaining on only in cells that become Müller glia or a specific subtype of bipolar cells
Vsx2:green fluorescent protein (GFP) is expressed first in all RPCs and later in bipolar and Müller cells in the developing zebrafish retina To investigate the in vivo role of Vsx2 in the zebrafish retina, we used Tg(vsx2:GFP) and Tg(vsx2:dsRed) transgenic zebrafish [26]
Summary
The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). Multipotent retinal progenitor cells (RPCs) either become restricted in their fate choice and proliferation potential or give rise to daughters that do so. These progenitors with restricted competence proliferate to a limited extent and differentiate into six classes of neurons and one type of glia in a fairly conserved histogenetic order [1]. Factors that influence the multipotent state of retinal progenitors should be expressed in all early retinal progenitors One such factor is the well-known transcription factor Pax, which is critical for early eye formation [4]. The conditional inactivation of this gene later in development restricts the competence of retinal progenitors such (page number not for citation purposes)
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