Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure
- Authors
- Stevens, C.B., Cameron, D.A., and Stenkamp, D.L.
- ID
- ZDB-PUB-110901-32
- Date
- 2011
- Source
- BMC Developmental Biology 11(1): 51 (Journal)
- Registered Authors
- Cameron, David A., Stenkamp, Deborah L., Stevens, Craig
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cell Proliferation
- Gene Knockdown Techniques/methods
- Morpholinos/genetics
- Receptors, Retinoic Acid/biosynthesis
- Retina/drug effects
- Retina/embryology*
- Retina/metabolism
- Retinal Cone Photoreceptor Cells/drug effects
- Retinal Cone Photoreceptor Cells/metabolism*
- Retinal Rod Photoreceptor Cells/drug effects
- Retinal Rod Photoreceptor Cells/metabolism*
- Retinoid X Receptor gamma/biosynthesis
- Signal Transduction
- Stem Cells/drug effects
- Stem Cells/metabolism*
- Tretinoin/metabolism
- Tretinoin/pharmacology*
- Zebrafish/embryology*
- Zebrafish/metabolism*
- PubMed
- 21878117 Full text @ BMC Dev. Biol.
BACKGROUND:
Retinoic acid (RA) is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. 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. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined.
RESULTS:
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. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. 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. The RA receptors RXRgamma and RARalphab are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RARalphab expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RARalphab also caused a reduced production of rods that was not restored by simultaneous treatments with RA.
CONCLUSIONS:
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 RARalphab receptor mediates the effects of endogenous, as well as exogenous RA, on rod development.