Author ORCID Identifier

Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation


Arts and Sciences



First Advisor

Dr. Ann C. Morris


Visual impairment ranges from mild forms that can be corrected with glasses to more severe cases that result in permanent loss of vision. Microphthalmia, anophthalmia, and coloboma (collectively referred to as MAC) account for 11% of cases of pediatric blindness and are a result of improper ocular morphogenesis. Retinitis Pigmentosa (RP) is a retinal degenerative disease that affects 1 in 3000 people worldwide. It is a progressive disorder that initially begins with loss of vision in low light settings due to rod photoreceptor degeneration but progresses to complete blindness upon loss of cone photoreceptors. Currently, there is no cure for either MAC or RP. Further insight into the essential components of ocular morphogenesis and the generation of retinal neurons could provide the base of knowledge needed for better patient screening and treatments like cell therapies.

The transcription factor Sox4 has previously been implicated as an important factor in both ocular morphogenesis and retinal development. Studies in humans, mice, zebrafish, and Xenopus have all linked Sox4 to microphthalmia and coloboma. Additional studies suggest a role for Sox4 in the generation of specific retinal neurons. Interestingly, in zebrafish, the absence of maternal sox4 transcripts in the developing embryo results in both microphthalmia and a reduction of rod photoreceptors. This suggests that Sox4 has a critical role early in specification of the eyefield that influences later retinal differentiation, however the precise functions of Sox4 during vertebrate ocular morphogenesis and retinal cell type differentiation remain unclear.

The studies presented in this Dissertation provide new insights into the role of Sox4 in eye development. Chapter 1 of this dissertation presents a review of ocular morphogenesis, retinal development, and what is currently known about the function of SoxC transcription factors and particularly Sox4 in embryonic and ocular development. In Chapter 2, a method to visualize ocular morphogenesis in living zebrafish embryos with high spatial and temporal resolution is demonstrated. Chapter 3 describes a detailed characterization of the ocular phenotypes of zebrafish sox4 mutants, and an in-depth analysis into the role Sox4 plays in both ocular morphogenesis and retinal differentiation. In vivo time lapse imaging, assays to assess cell proliferation and cell death, and immunohistochemistry to detect retinal cell types were used to characterize the phenotypes of microphthalmia and a reduction of rod photoreceptors in the sox4 mutants. Furthermore, scRNA-seq was used to address if there is any heterogeneity prior to ocular morphogenesis that may affect later retinal differentiation. Chapter 4 will address the impact of findings in the sox4 mutants, and the suggested future directions for this project. Finally, an appendix chapter will include additional data about a possible role for Sox4 in neural crest cells.

Digital Object Identifier (DOI)

Funding Information

Research reported in this publication was supported by the Office of The Director of the National Institutes of Health under Award Number S10OD020067 and by National Institutes of Health award R01EY021769 (to A.C.M.).

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