During the age of non-avian dinosaurs, ancestors of present-day mammals were likely small insectivores, relegated to nocturnal
and subterranean niches. This nocturnal "bottle-neck" is postulated as a driving force of numerous physiological and sensory adaptations
including those of the visual system. The consequences of structural mutations of opsins upon spectral sensitivity and environmental
adaptation have been studied in great detail, but lacking is knowledge of the potential influence of alterations in gene regulatory
networks upon the diversity of cone subtypes and the variation in the ratio of rods and cones observed in diurnal and nocturnal species.
Exploiting photoreceptor patterning in cone-dominated zebrafish, we uncovered two independent mechanisms by which the sine oculis homeobox
homolog 7 (six7) regulates photoreceptor development. In a genetic screen, we isolated the lots-of-rods-junior (ljrp23ahub) mutation that
resulted in an increased number and uniform distribution of rods in otherwise normal appearing larvae. Sequence analysis, genome editing
using TALENs and knockdown strategies confirm ljrp23ahub as a hypomorphic allele of six7, a teleost orthologue of six3, with known roles
in forebrain patterning and expression of opsins. Based on the lack of protein-coding changes and an identified deletion of a conserved
sequence about 40 kb upstream of six7 loci, a cis-regulatory mutation is proposed as the basis of the reduced expression in ljrp23ahub.
Comparison of the hypomorphic and knock-out alleles provides evidence of two independent roles in photoreceptor development. EdU and PH3
labeling show that the increase in rod number and uniform distribution is associated with extended mitosis of photoreceptor progenitors,
and TUNEL suggest that the lack of green cones is the result of cell death of the cone precursor. These data add six7 to the small but
growing list of genes essential for specification and patterning of photoreceptors in non-mammalian vertebrates, and form the basis of a
model that underscores the potential of alterations in transcriptional regulation as a mechanism underpinning photoreceptor variation
across species. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the Doctor
of Philosophy. / Spring Semester 2016. / March 14, 2016. / development, evolution, photoreceptors, retina, TALENs, zebrafish / Includes bibliographical references. / James M. Fadool, Professor Directing Dissertation; Jamila I. Horabin, University Representative;
Brian P. Chadwick, Committee Member; Hank W. Bass, Committee Member; Wu-Min Deng, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_360446 |
| Contributors | Sotolongo-Lopez, Mailin (authoraut), Fadool, James Michael (professor directing dissertation), Horabin, Jamila I. (university representative), Chadwick, Brian P. (committee member), Bass, Hank W. (committee member), Deng, Wu-Min (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Biological Science (degree granting department) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource (99 pages), computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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