PgmNr Z6220: Genetic regulation of photoreceptor specification in zebrafish as a model for understading photoreceptor variation in diurnal species.

Authors:
J. M. Fadool; M. Sotolongo-Lopez


Institutes
Florida State University, Tallahassee, FL.


Abstract:

The visual system is highly adapted to convey detailed ecological and behavioral information essential for survival of a species. The retinas of the majority of vertebrates are dominated by 4 cone subtypes sensitive to UV, blue, green and red wavelengths of light. However, much of our understanding of photoreceptor development is based on findings from mammalian models which are highly adapted to dim light conditions with rods vastly outnumbering the sparse and less diverse cone subtypes and thus fail to explain the tremendous diversity of cone subtypes and variation of rod and cone numbers in many species. The spatial patterning of zebrafish photoreceptors combined with classical genetics and emerging gene-targeting technologies, offer unprecedented opportunities to investigate photoreceptor biology. In the larval zebrafish retina the four cone subtypes grossly outnumber the far fewer, assymetrically distributed rods. Previously, we showed that loss-of-function and hypomorphic alleles of tbx2b result in an increase in the number of rods across the retina and a decrease in the number of UV-sensitive cones. Subsequently we showed that knockdown of six7 results in a nearly identical rod phenotype, and knockout alleles result in the additional loss of the green-sensitive cone subtype. We report that hypomorphic alleles of six7 and tbx2b are additive in their effects upon the number of rods. In wildtype larvae, cones outnumber rods 20:1, but in double mutants, the rods account for approximately 40% of the total number of photoreceptors. Furthermore, spatial pattern analysis indicates that the rods are uniformly distributed across the mutant retinas. Genome sequence analysis of the hypomorphic allele identified the deletion of a putative cis-regulatory module that may underlie the photoreceptor alterations. Lastly, additional gene knockdown approaches show the potential of epistatic interactions to drive further changes in rod and cone ratios. These data demonstrate the effects of subtle alteration of gene expression upon photoreceptor patterning, and the potentail for alterations in the gene-regulatory network as a driving forces underlying variation in rod and cone numbers across species.



ZFIN Genetics Index
1. T-box 2b
2. SIX homeobox 7