Newts are amazing amphibians that are capable of regenerating many body parts including their limbs, brain, heart, and many eye parts. Specifically, our lab focuses on the newts’ ability to regenerate their lens. Following removal of the lens, cells from the upper portion of the iris (dorsal iris) lose their identity as iris cells and transform into lens cells- a completely different cell type. Interestingly, cells from the bottom iris (ventral iris) are unable to regenerate a lens. Our lab investigates the molecular mechanisms that govern the differences between the regeneration-competent dorsal iris and its morphologically indistinguishable counterpart, the ventral iris. Using transcriptomic and proteomic analysis, Ephrins, a family of proteins, were identified as differentially expressed between the irises.
While the Eph/Ephrin pathway is known to play a critical role in development, migration, and cancer, its role in lens regeneration is unknown. To investigate this, we surgically removed the lens and inhibited Eph receptors individually by injecting class-specific inhibitors into the eye. While the inhibition of the “B” class of Ephrins did not induce a phenotype, the inhibition of the “A” class of Ephrins resulted in the induction of ventral lens regeneration in vivo. Similar results were observed in vitro using separated dorsal and ventral iris segments. Additionally, western blots have been optimized using newt tissue and are being used to analyze the activation or inhibition of the downstream cascade of Ephrins following their inhibition.
By understanding how we induced regeneration in a tissue that was previously thought to be incapable of doing so, we can piece together the puzzle of regeneration in higher vertebrates, which could hold great clinical and therapeutic significance. I intend to pursue an MD/PhD in cell and molecular biology and an understanding of the molecular events governing lens regeneration will be very beneficial in this career.
Author: Alyssa Miller
Advisors: Dr. Katia Del Rio-Tsonis, Dr. Tracy Haynes, Dr. Anthony Sallese, and George Tsissios, Department of Biology