Alexa Maupin
Pronouns: she/her
Research Mentor(s): Donna Martin
Research Mentor School/College/Department: Pediatrics-Genetics / Medicine
Program: UROP
Session: Session 2 (10:00am – 10:50am)
Authors: Alexa Maupin, Jingxia Gao, Jelka Cimerman, Jennifer Skidmore, Donna Martin
Abstract
BACKGROUND: In this study, we explored the interaction between the genes Sox2 and Chd7, which are critical to early inner ear development. We know that the loss of a single copy of either gene disrupts organ and tissue development, however, Sox2 and Chd7 interactions in ear development have yet to be thoroughly researched. OBJECTIVE: Hearing loss and balance disorders caused by genetic factors pose significant challenges to patients, yet current molecular therapies do not provide effective treatment. The findings from our study could be used to develop new targets for molecular therapies in the future. DESIGN/METHODS: We observed the interaction between Sox2 and Chd7 using Chd7Gt/+, Sox2CreER/+, and Sox2flox/flox mice. Primary and secondary antibodies were used to identify Sox2 and Chd7 expression, while paint-fill was used to observe the inner ear. At postnatal day 1 (P1), the mouse pup cochleae were dissected, stained with whole-mount assays, and imaged with confocal microscopy. Microdissected E10.5 otocysts were processed for RNA sequencing. RESULTS: We discovered that Sox2 and Chd7 are co-expressed as the otocyst and cochleovestibular ganglion are developing. While Chd7 expression is independent of that of Sox2, Sox2 relies on Chd7 for normal expression at E10.5 in the otocyst. Chd7Gt/+; Sox2CreER/+, or double heterozygous, mice died shortly after birth and had deformations in the inner ear. Notably, there were malformations in the semicircular canals and shortened cochlea. Thus, we found that Sox2 and Chd7 expression is strictly regulated in inner ear development and that disruptions to their interactions also disrupt normal development of the inner ear.
