Molecular bases of sensorineural
development. transcriptional regulation of retinal and inner ear
development
Our research interests center on
understanding the molecular events that lead to the determination. differentiation and survival of the highly specialized sensory cells and
neurons. The mammalian sensory system carries external and internal
sensory information to the central nervous system. where it is processed
to coordinate motor responses. The establishment of these sensory
circuits in the adult depends critically on the generation of distinct
neuronal types and sensory receptors at proper times and positions
during embryogenesis as well as on their maintenance throughout life.
Despite the importance of sensory cells/neurons. however. the molecular
basis of their formation and survival is still poorly understood. My
laboratory employs a variety of molecular genetic and bioinformatics
approaches to identify and study transcription and other regulatory
factors that are required for programming development of the retina. inner ear. somatosensory ganglia. spinal cord. and brain. A major focus
of our work is to develop animal models to study roles of transcription
factor genes during normal sensorineural development. as well as to
elucidate how mutations in these genes cause sensorineural disorders
such as blindness and deafness.
My laboratory utilizes two general approaches to understand the
biological roles that a transcription factor gene plays during
vertebrate neurogenesis. One is a loss-of-function approach involving
targeted gene disruption in mouse embryonic stem (ES) cells to produce
mice deficient for the gene of interest. The other is a gain-of-function
approach involving plasmid/retrovirus-mediated overexpression of the
gene of interest in the chick and mouse embryonic tissues. These
complementary approaches have allowed us to identify a number of
transcription factors including Foxn4. Barhl and Brn3 as crucial
regulatory factors that are required for fate commitment. differentiation and/or survival of various sensory cells and neurons.
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