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D. McNeill, C. J. Sheely, R. L. Brown, S. Hattar; Development and Targeting of Melanopsin-Expressing Retinal Ganglion Cells and Their Projections in the Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2907.
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The mammalian eye detects light to form images and modulate light dependent physiological processes. All light signals are conveyed to the brain via the retinal ganglion cells (RGCs), which are the sole output neurons of the retina. 1-2% of RGCs are intrinsically photosensitive (ipRGCs) and express the photopigment melanopsin. A previously generated mouse that contains a tau-LacZ reporter under control of the melanopsin promoter revealed that ipRGC axons project to brain targets responsible for circadian rhythms, such as the suprachisamatic nucleus (SCN) and intergeniculate leaflet (IGL), as well as other brain regions involved in light dependent physiological functions. The ipRGCs comprise a population of newly identified photoreceptors whose developmental characteristics are largely unknown. The purpose of this study is to determine when ipRGCs express melanopsin and when they innervate their brain targets.
We used X-Gal staining of coronal sections from the melanopsin-tau-LacZ reporter mouse to specifically label ipRGC axonal projections throughout development. Immunostaining was performed using a rabbit N-terminal anti-melanopsin antibody, and a chicken anti-beta-galactosidase antibody (Chemicon).
According to X-gal labeling of Melanopsin-tau-LacZ mice, ipRGC axons reach the chiasm ventral to the SCN by embryonic day 16.5 (E16.5), but do not begin to innervate the SCN until postnatal day 2.5 (P2.5). At E16.5, ipRGC axons have also reached the lateral geniculate complex, but do not show defined innervation of the IGL until about P5. Although transcripts of melanopsin have been shown as early as E10.5, X-gal labeling of ipRGCs is first detected at E15.5 and melanopsin immunostaining at E16.5.
ipRGCs express melanopsin and project axons to the SCN and the IGL areas embryonically, but they pause and do not innervate the SCN and IGL until after birth. This pause is not observed in the conventional targeting of visual centers by the RGCs and indicates that the innervations by ipRGCs may differ from conventional RGCs.
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