CSB Special Seminar: Kathryn Cheah, PhD, Thursday, March 20, 2025, Munzer, 1:30 PM!
The Department of Chemical and Systems Biology Presents
Special Seminar
Kathryn Cheah, Ph.D.
Emerita Chair Professor of Biochemistry
University of Hong Kong
Thursday, March 20, 2025
1:30 PM – 2:30 PM
Munzer Auditorium
Talk Title: “SOX control of sensory and non sensory cell fate in the otic vesicle defines development of the inner ear”
Talk Abstract: The proper development of the vertebrate inner ear, including the specification of sensory organs and non-sensory structures like the endolymphatic duct and sac, is essential for hearing and balance. Patterning is established early in the otic vesicle (OV), where distinct regions are predetermined to form specific sensory and non-sensory components. Understanding the molecular mechanisms governing these domains is critical for insights into hearing and balance impairments. My seminar highlights the role of SOX family transcription factors in inner ear development, particularly in controlling sensory and non-sensory cell fate. Using a mouse model of the SOX9Y440X/+ mutation, which causes campomelic dysplasia and deafness, we demonstrate the essential roles of SOXE factors, SOX9 and SOX10, in non-sensory endolymphatic system development. We also identify SOX9-WNT antagonism as a key mechanism regulating SOX10 activity in mouse and human otocysts, influencing endolymphatic cell fate. In contrast, SOX2 is crucial for sensory organ development, with its gradient expression (high ventromedially, low dorsally) in the OV being pivotal. Studies of Sox2 hypomorphic mutants (Yellow submarine and Light coat and circling) reveal disrupted long-range enhancers controlling SOX2 dosage and temporal expression, leading to sensory organ defects and deafness. Single-cell analyses and lineage tracing show that disrupted SOX2 expression causes a fate switch to non-sensory endolymphatic sac cells. Together, SOXE and SOX2 factors act as master regulators of cell fate determination during inner ear development.