Research

     CONTROL OF NERVE CELL
       DIFFERENTIATION

     GENETIC DETERMINANTS
       OF NEURONAL NUMBER

     PATTERNED NERVE CELL
       DISTRIBUTIONS IN THE
       BRAIN

     RPE SIGNALLING AND
       AXONAL MISROUTING AT
       THE OPTIC CHIASM

Genetic Determinants of Neuronal Number

        The cellular architecture and connectivity of the vertebrate retina is remarkably conserved across species. What distinguishes these retinas most is the relative numbers of each of the different cell types. Even within a species, there is often conspicuous variation in the size of a neuronal population, suggesting the presence of allelic variants that modulate proliferation, fate determination or cell survival.

        We have recently demonstrated a large, natural, variation in the number of cone photoreceptors, horizontal cells and dopaminergic amacrine cells in different inbred strains of mice. By using recombinant inbred mice, we have mapped this variation in phenotype (cell number) to genomic loci where polymorphic genes contributing to that variation must be present. Candidate genes within such "quantitative trait loci" (QTL) can then be tested through gene-targeting strategies.

        One particularly attractive aspect of using recombinant inbred strains of mice derived from parental strains differing in the phenotype of interest is that it permits comparisons with other databases derived from the same collection of genetically identical recombinant inbred strains. These include gene expression databases, through which one can seek direct correlations between variation in phenotype with transcriptional activity in the retina. Using these approaches, we have identified candidate polymorphic genes underlying the natural variation in these three cell types.