Thyroid hormone (TH) is crucial for many biological processes, including the development of the auditory system. Appropriate thyroid hormone signaling is important for the development of the cochlea, leading to the successful onset of hearing. More specifically, TH influences the timing of remodeling of the greater epithelial ridge (GER), a transient cochlear structure that secretes proteins that contribute to the formation of the tectorial membrane. Developmental hypothyroidism results in delayed GER regression, whereas excess TH results in premature remodeling. Both conditions result in deafness. However, it is unknown how TH mediates GER remodeling. Expression profiling identified APOBEC3 (A3) as a GER-expressed gene responsive to TH. A3 is an enzyme that edits nucleic acid sequences and has been shown to prevent viral replication via deamination mechanisms in humans. Mouse A3 (mA3) can prevent viruses, but its mode of action remains unclear. Interestingly, human A3 is genotoxic if overexpressed. If mA3 is able to induce apoptosis similarly to that of human A3, then it can be speculated that mA3 expression in developing systems may drive apoptosis-induced morphogenesis.
We hypothesize TH positively regulates mA3 expression in the GER to promote GER remodeling. To test our hypothesis, mA3 mRNA was quantified via qRT-PCR in post-natal day 2 hyperthyroid pups (T3 injected) and compared to control pups. Results indicated that the mA3 mRNA expression increases significantly upon T3 injection compared to the control, following a similar trend as tectorin-β mRNA expression, a gene controlled by TH. Localization of mA3 via in situ hybridization indicate that mA3 is expressed in the GER, interdental cells, and in the spiral ganglion of the cochlea. mA3 mRNA expression does not appear to change throughout the developmental period investigated (P0-P7) in the interdental cells and the spiral ganglion. Expression in the GER is observed until P5, before the GER regresses. Given that mA3 is expressed in the GER and its expression is increased with T3 injections, it supports the idea that mA3 may be involved in GER regression. mA3 may also be expressed in macrophages and involved in the protection against viruses, as well as the maintenance of cochlear structures.
Date of Degree
Master of Science (MS)
Program of Study
Science, Engineering and Technology
Santiago, M. (2023). APOBEC3 regulation by thyroid hormone [Master’s thesis, Minnesota State University, Mankato]. Cornerstone: A Collection of Scholarly and Creative Works for Minnesota State University, Mankato. https://cornerstone.lib.mnsu.edu/etds/1282/
Available for download on Wednesday, May 07, 2025