【摘 要】
：
Frizzled3 (Fzd3),a key Wnt receptor of Wnt/Planar Cell Polarity signaling in mammals,contributes to axon guidance of some retinal ganglion cells.Moreover,Frizzled,the ortholog of Fzd3 in Drosophila,re
【机 构】
：
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of C
【出 处】
：
Joint Symposium of 2016 International Neural Regeneration Sy
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Frizzled3 (Fzd3),a key Wnt receptor of Wnt/Planar Cell Polarity signaling in mammals,contributes to axon guidance of some retinal ganglion cells.Moreover,Frizzled,the ortholog of Fzd3 in Drosophila,regulates ommatidia arrangement by directing their relative positions.These evidence suggest an important role of Fzd3 in visual development.However,its de-velopmental functions in the retina,the initial sensor of the visual system,remain elusive.The present study explores the role of Fzd3 in retinal development in detail by focusing on rod bipolar cells.We used the Cre-loxP system to remove Fzd3 from Isl1 positive cells of the Isl1-Cre;Fzd3f/-conditional knock-out mice.Electroretinogram recording showed significantly lower b-wave amplitudes and b-to a-wave ratios in Isl1-Cre;Fzd3f/-than in control (Isl1-Cre;Fzd3f/+) mice,indicating compro-mised retinal light response upon Fzd3 inactivation.In Isl1-Cre;Fzd3f/-retina,Fzd3 was highly expressed and knocked out in some ON-bipolar cells,including all protein kinase Ca-positive rod bipolar cells.Focusing on rod bipolar cells,we found that theIsl1-Cre;Fzd3f/-retina disclosed obvious defects in morphogenesis.Their somas were organized irregularly in the tangential plane,clustered abnormally with round shape and random orientation.Their dendrites overshot into the outer nuclear layer frequently with branching depressed.Many rod bipolar cell dendrites failed to invaginate the rod spherules,and the density of rod ribbons was significantly reduced.Defects in synaptic connection impaired light transmission from rods to rod bipolar cells,which resulted in decreased b-to a-wave ratios and b-wave amplitudes in electroretinogram recording.In conclusion,Fzd3 is required for shaping rod bipolar cell somas patterning and dendritic maturation,as well as the structural and functional connectivity between rods and rod bipolar cells.These results highlight novel functions of Fzd3 in the retinal,visual,and even neural development besides axon guidance.
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