Research Projects

Establishing the morphology and cytoarchitecture of an epithelium is an important aspect of tissue differentiation and greatly influences organ function. The auditory sensory organ, the cochlea, comprises mechanosensory hair cells, which are the auditory receptors of the organ, and glial support cells, which provide trophic and structural support for hair cell function. The cellular cytoskeleton determines structural integrity. Since much focus is placed on the structural aspects of stereocilia cytoskeletal formation and signaling in the hair cells, little attention has been given to the cell signaling and cellular processes that occur in the support cells. As a result, how structural formation, or cytoarchitecture of the support cells is established is not well understood. Recent studies showed that a mutation in a gene encoding a cytoskeleton binding protein, results in hearing loss in humans. Mouse models showed a mild buckling of the structure of support cells. This highlights the important, but under-appreciated role that the support cells play in hearing. Through transcriptomic sequencing, we identified a novel gene, Shroom1. SHROOM1 belongs to the SHROOM family of proteins that are F-actin cytoskeleton binding proteins. We found that Shroom1 was expressed in the support cells of the sensory epithelium, but not in the hair cells. Thus, we hypothesize that SHROOM1 is an F-actin binding protein that regulates the support cell cytoskeleton and cell adhesion during differentiation. To test our hypothesis and investigate its function, we will perform gene over-expression experiments in 3-dimensional whole cochlear organ cultures to analyze the impact of its gain-of-function. We also generated a knockout (KO) mouse model to analyze the impact of its loss-of-function. Our preliminary data show that Shroom1 expression is knocked out in the KO mouse model and a phenotype is present. We will characterize this mutant mouse model and using both approaches, we will explore the potential molecular mechanisms underlying support cell structure. By investigating SHROOM1 function, we will have a better understanding of how the structures of support cells are attained and when disrupted, leads to hearing loss.