Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure.
Retinoic acid (RA) is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. The vertebrate retina forms from a neuroepithelium that develops into a complex, layered structure of neurons consisting of
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the ganglion cell layer (GCL); the inner nuclear layer (INL), composed of the amacrine, horizontal, and bipolar cells; and the outer nuclear layer (ONL), composed of the light-sensing photoreceptors. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones.Treatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA.
These data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate decision. The RARαb receptor mediates the effects of endogenous, as well as exogenous RA, on rod development.
Authors: Craig B Stevens, David A Cameron and Deborah L Stenkamp.
Source: BMC Developmental Biology 2011, 11:51
DOI: 10.1186/1471-213X-11-51 30 August 2011
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