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Patrick William Keeley, Jason J Kim, Ace J St. John, Benjamin E Reese; Variation in cellular density is not predictive of the variation in mosaic regularity for the VGluT3+ amacrine cell population. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1780.
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© ARVO (1962-2015); The Authors (2016-present)
Several interrelated features of neuronal populations ensure uniform participation in the local circuitry of the nervous system, including cellular density, spacing, and dendritic spread. The extent to which these features rely on common developmental processes remains unknown. The VGluT3+ amacrine cell (VG3 AC) population in the mouse retina undergoes a substantial amount of Bax-mediated apoptosis during development, being a potential mechanism for establishing the final number of cells as well as the regularity in their distribution. We therefore explored the degree to which these two traits are related.
Retinas were collected from Bax-knockout (KO) and Bax-wildtype (WT) mice, as well as from 26 strains of the AXB/BXA recombinant inbred (RI) set of mice. Wholemount retinas were immunolabeled to reveal the population of VG3 ACs, and eight sampling fields were chosen from which cell densities and somal positions were recorded. The latter were used to determine the regularity indexes for each field, which were compared to random distributions matched in density and constrained by soma size. Data collected from the RI strains were used to identify quantitative trait loci (QTL) using GeneNetwork.org.
VG3 AC density is increased more than three-fold in Bax-KO retinas, and the patterning of their cell bodies is comparable to that of random distributions, indicating that Bax-mediated cell death must be spatially regulated to achieve the distribution seen in Bax-WT retinas. We next asked whether this inverse relationship between density and mosaic regularity was present across the RI strains, which have been shown to exhibit substantial variation in VG3 AC number. While regularity also varied across the strains, it was not significantly correlated to density. Additionally, the variation observed for each trait mapped to distinct genomic loci.
Bax-mediated apoptosis is responsible for eliminating a large proportion of VG3 ACs, the loss of which transforms their patterning from a random to an ordered mosaic. The analysis of the RI strains, however, indicates that the variation in both cell number and mosaic regularity cannot be reduced to allelic variants modulating a single biological process. Investigation of the two identified QTL should provide insights into the different mechanisms that shape these demographic features of this population.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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