Date of Award

12-2018

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Wendy S. Beane

Second Advisor

Dr. John A. Jellies

Third Advisor

Dr. John M. Spitsbergen

Fourth Advisor

Dr. Kelly Ai-Sun Tseng

Abstract

Although humans lack the ability to regenerate complete organs and limbs following amputation or injury, there are many other species (both vertebrates and invertebrates) that can. Significant advances have been made in understanding the genetic mechanisms that regulate organ regeneration in these species, including regeneration of eye tissues such as the lens and retina. Planarians are an established historical model used to study regeneration due to their ability to regenerate any organ, including the eye. With recent advances in molecular genetic analyses, planarians are now an emerging model for the specific study of eye regeneration mechanisms. Furthermore, regeneration of the planarian eye is an ideal system for investigating regenerative morphology, in other words how tissue size, shape, and placement is established during regeneration. However, comparatively little is known about the physiology of planarian photoreception or the mechanisms that regulate eye regrowth. These fundamental aspects must be understood in order to increase the effectiveness of the planarian eye regeneration model.

Our data has revealed that planarians have complex phototactic responses and display differential behaviors to specific wavelengths of light, including ultraviolet and infrared. This information is critical because regeneration studies previously determined functional recovery of the visual system based on planarian responses to white light. As white light is a composite of many wavelengths, this may have masked complex behaviors or resulted in inconsistent results between studies. We also found that similar to other invertebrates, planarians are capable of responding to light using mechanisms outside of the eye, inputs that could also confound analyses of ocular responses. Our data show that extraocular behavioral responses in planarians are regulated in part by a homolog of the transient receptor potential channel A1 (TRPA1), a mechanism previously only identified in Drosophila.

Using this expanded understanding of planarian photoreception, we investigated the cellular mechanisms required for planarian eye regeneration. We have identified a potential cell signaling pathway that includes the vacuolar ATPase (V-ATPase) ion channel, Notch, and apoptosis. We found that similar pathway components were also required for eye regrowth in developing tadpoles, suggesting evolutionarily conserved mechanisms are required for eye regeneration in two very different animal models. Together, the data presented in this work increases our understanding of planarian photoreception and provides evidence that ancestral mechanisms may be required for eye regeneration.

Access Setting

Dissertation-Campus Only

Restricted to Campus until

12-2023

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