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Benjamin Reese, Patrick Keeley, Irene Whitney, Sarra Borhanian; Genetic Control of Rod Bipolar Cell Number and the Homotypic Regulation of Dendritic Field Size. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5148.
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© ARVO (1962-2015); The Authors (2016-present)
Unlike other retinal cell types, the size of the rod bipolar cell (RBC) population does not differ between the C57BL/6J (B) and A/J (A) strains of mice, and their dendritic field areas do not differ. The present study has examined these traits, in recombinant inbred (RI) strains and in F1 offspring derived from these two parental strains, to assess whether genetic variants modulate cell number, and if dendritic field size varies accordingly.
Retinas from 24 RI strains and from F1 and parental strains (122 mice) were labeled using antibodies to PKC and subsequently quantified (while blind to strain) in order to estimate total RBC number. Quantitative trait locus (QTL) mapping was conducted at GeneNetwork.org. Single RBCs in two strains were injected with DiI for morphometric analysis (10 mice).
RBC number within any strain showed modest variability (average CoV = 0.05), yet large variation was detected across the RI strains, from 202,415 cells in the lowest strain (AXB15) to 254,176 cells in the highest (BXA7). This heritable variation was mapped to multiple loci across the mouse genome, including two large-effect QTLs on Chr 4 and 8, where A alleles at the former locus and B alleles at the latter correlated with an increase in RBC number across the strain-set. The estimated magnitude of each QTL was 18,400 and 19,300 cells, respectively. As the population of RBCs in the F1 offspring was 16% greater than in the parental A strain, these two strains were used to examine the effects of variation in cell number upon morphological differentiation. RBC soma size was not different, but the dendritic field areas of the F1 were significantly smaller than those in the A strain. Curiously, the total number of dendritic terminal endings upon these narrower F1 dendritic fields was slightly but significantly larger, suggesting the presence of a larger number of rod photoreceptors afferent to these rod bipolar cells, and is consistent with the thicker ONL in the F1 cross.
Rod bipolar cell number is a complex trait controlled by multiple genetic variants distinguishing the B and A strains, the effects of which sum to produce comparable numbers in the parental strains. Where variation in the size of the RBC population is present between strains, this cell type appears to modulate dendritic growth in response to homotypic density, maintaining a constant dendritic coverage factor.
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