How neuronal processes develop and establish proper wirings with their synaptic partners is one of the fundamental questions of neuroscience. The vertebrate retina is an outstanding model system for studying dendritic development and neuronal connections. One of the critical visual functions, color vision, requires precise wiring of retinal neurons. In the mouse retina, there are two types of cone photoreceptors, the short wavelength sensitive cones (S-cones), which only express S-opsin, and the long wavelength sensitive cones (M-cones), many of which co-express S-opsin. In order to generate color opponency, signals from these two types of cones have to be segregated before they are contrasted at the ganglion cell level. S-cones only account for 2-5% of the total cone population. Thus, the downstream S-cone bipolar cells (SCBCs) face the daunting task of seeking out very sparse S-cones from a majority of M-cones. The outcome is that SCBCs develop a very unique dendritic arbor with long, meager dendrites that contact a handful of S-cones. This distinctive connection between S-cones and SCBCs makes it an excellent model system to study how presynaptic neurons affect the dendritic development and synaptic targeting of postsynaptic neurons. We took advantage of an animal model (Thrb2-/- mice), where M-opsin expression is abolished and all M-cones are turned into blue cones and asked how this alteration in number and type of cone afferents will affect the dendritic development and synapse formation of SCBCs. We obtained Clm/Thrb2+/+, Clm/ Thrb2+/- and Clm/Thrb2-/- mice and compared dendritic morphology of SCBCs from these mice. We found that the number of SCBCs from Thrb2-/- mice is comparable to that in wildtype and Thrb2+/- mice. Morphologically, SCBCs from Thrb2-/- mice are indistinguishable from those in wildtype and Thrb2+/- mice in terms of length of dendrites, number of dendritic branches and number of cone contacts. Our results indicate that dendritic development of SCBCs appears to be independent of the afferent input from S-opsin expressing cones, and that true S-cones may be specified by other transcription factors than Trb2, which controls S-opsin expression. In the past year, we continued our work by looking at the flip side of the coin. In Sopsin-/- mice, Sopsin gene is knocked out, hence all the cones are M-cones by the criteria of their opsin expression. We obtained Clm;Sopsin-/- and Clm;Thrb2-/-;Sopsin-/- (DKO) mice and compared dendritic morphology of SCBCs in these mice. mCAR expression is retained in these mice, and are therefore used to label the cone pedicles. We found that the numbers of SCBCs in Thrb2-/- and Sopsin-/- and DKO mice are comparable to that in wildtype. Morphologically, SCBCs in Thrb2-/- and Sopsin-/- mice are indistinguishable from those in wildtype in terms of length of dendrites, number of dendritic branches and number of cone contacts. These results again indicate that dendritic development of SCBCs appears to be intrinsic and independent of the opsin expression of the afferent input, and that true S-cone identity may be specified by factors other than the expression of Sopsin.
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