Elucidating the Role of Pten in Retinal Development and Pattern Formation
Abstract
The retina is a neural tissue that is a part of the central nervous system that resides at the back of the eye. It serves as the first sensory processing center of the visual environment. All of the cell types in the retina have been well-characterized, and their physiological functions are generally well described. As a member of a developmental biology laboratory, I have been interested in understanding the factors that dictate the events that regulate the precisely orchestrated development of the retina, such as the proliferation of neural progenitors, differentiation of neuronal cell types, migration of neuronal cells to their designated destinations, and the formation of synaptic connections.
When this project was undertaken, very little was understood about the role of the Pten (phosphatase and tensin homologue) phosphatase and PI3K (phosphatidylinositol 3-kinase) signaling pathway in the retina. While PI3K signaling was known to be responsible for proliferation, differentiation, cell death, migration, neurite outgrowth, and synapse formation in different regions of the developing CNS, its role in the retina was understudied. In this thesis, I describe experiments in which I deleted Pten gene in the mouse retina with a conditional knockout (cKO) approach to elucidate its role in retinal development. During early retinal development, I found that Pten is required to regulate the differentiation of retinal amacrine cells and rod photoreceptors. I focused on amacrine cells, and found that Pten regulates amacrine cell number by modulating three different signaling pathways, Akt, TgfβII, and Erk (Chapter 3). Furthermore, I found that the deletion of Pten in the peripheral and not central retina created an animal model of Pten hamartoma tumor syndrome (PHTS), with the central ‘wild-type’-like retinal tissue forming a hamartoma-like lesion (Chapter 4). Finally, I described a role for Pten at later stages of the retinal development in regulating cellular patterning (Chapter 5). Specifically, I observed several examples of mispatterning in Pten cKO retinas, including an expansion of the inner plexiform layer, and the disrupted organization of amacrine cells in both the radial and tangential planes. I also investigated genetic relationships between Pten and the cell adhesion molecule Dscam in guiding cellular positioning, as the deletion of Dscam largely phenocopies the Pten cKO in the retina, and I found for the most part that they act in separate pathways. In summary, I have significantly expanded our knowledge of Pten function in the developing retina during my PhD studies.
Description
Keywords
Neuroscience
Citation
Tachibana, N. (2017). Elucidating the Role of Pten in Retinal Development and Pattern Formation (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25869